Esophageal Microenvironment: From Precursor Microenvironment to Premetastatic Niche

References

• Haiyu Z, Xiaofeng P, Xiangqiong M, et al. Incidence and survival changes in patients with esophageal adenocarcinoma during 1984–2013. Biomed Res Int. 2019;2019:7431850. doi:10.1155/2019/743185031915702
   PubMed Web of Science ®Google Scholar
• Gupta B, Kumar N. Worldwide incidence, mortality and time trends for cancer of the oesophagus. Eur J Cancer Prev. 2017;26(2):107–118. doi:10.1097/CEJ.000000000000024927014938
   PubMed Web of Science ®Google Scholar
• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69(1):7–34. doi:10.3322/caac.2155130620402
   PubMed Web of Science ®Google Scholar
• Pennathur A, Gibson MK, Jobe BA, Luketich JD. Oesophageal carcinoma. Lancet. 2013;381(9864):400–412. doi:10.1016/S0140-6736(12)60643-623374478
   PubMed Web of Science ®Google Scholar
• Kim JA, Shah PM. Screening and prevention strategies and endoscopic management of early esophageal cancer. Chin Clin Oncol. 2017;6(5):50. doi:10.21037/cco.2017.09.0529129090
   PubMedGoogle Scholar
• Barsouk A, Rawla P, Hadjinicolaou AV, Aluru JS, Barsouk A. Targeted therapies and immunotherapies in the treatment of esophageal cancers. Med Sci (Basel). 2019;7(10):100.
   PubMedGoogle Scholar
• Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. Annu Rev Immunol. 2004;22(1):329–360. doi:10.1146/annurev.immunol.22.012703.10480315032581
   PubMed Web of Science ®Google Scholar
• Wang M, Zhao J, Zhang L, et al. Role of tumor microenvironment in tumorigenesis. J Cancer. 2017;8(5):761–773. doi:10.7150/jca.1764828382138
   PubMed Web of Science ®Google Scholar
• Altorki NK, Markowitz GJ, Gao D, et al. The lung microenvironment: an important regulator of tumour growth and metastasis. Nat Rev Cancer. 2019;19(1):9–31. doi:10.1038/s41568-018-0081-930532012
   PubMed Web of Science ®Google Scholar
• Rojas A, Araya P, Gonzalez I, Morales E. Gastric tumor microenvironment. Adv Exp Med Biol. 2020;1226:23–35.32030673
   PubMed Web of Science ®Google Scholar
• Perus LJM, Walsh LA. Microenvironmental heterogeneity in brain malignancies. Front Immunol. 2019;10:2294. doi:10.3389/fimmu.2019.0229431632393
   PubMed Web of Science ®Google Scholar
• Höpken UE, Rehm A. Targeting the tumor microenvironment of leukemia and lymphoma. Trends Cancer. 2019;5(6):351–364. doi:10.1016/j.trecan.2019.05.00131208697
   PubMed Web of Science ®Google Scholar
• Baatar D, Jones MK, Tsugawa K, et al. Esophageal ulceration triggers expression of hypoxia-inducible factor-1 alpha and activates vascular endothelial growth factor gene: implications for angiogenesis and ulcer healing. Am J Pathol. 2002;161(4):1449–1457. doi:10.1016/S0002-9440(10)64420-312368217
   PubMed Web of Science ®Google Scholar
• Ling FC, Khochfar J, Baldus SE, et al. HIF-1alpha protein expression is associated with the environmental inflammatory reaction in Barrett’s metaplasia. Dis Esophagus. 2009;22(8):694–699. doi:10.1111/j.1442-2050.2009.00957.x19302222
   PubMed Web of Science ®Google Scholar
• Suchorolski MT, Paulson TG, Sanchez CA, Hockenbery D, Reid BJ. Warburg and crabtree effects in premalignant Barrett’s esophagus cell lines with active mitochondria. PLoS One. 2013;8(2):e56884. doi:10.1371/journal.pone.005688423460817
   PubMed Web of Science ®Google Scholar
• Quante M, Graham TA, Jansen M. Insights into the pathophysiology of esophageal adenocarcinoma. Gastroenterology. 2018;154(2):406–420. doi:10.1053/j.gastro.2017.09.04629037468
   PubMed Web of Science ®Google Scholar
• Stairs DB, Kong J, Lynch JP. Cdx genes, inflammation, and the pathogenesis of intestinal metaplasia. Prog Mol Biol Transl Sci. 2010;96:231–270.21075347
   PubMed Web of Science ®Google Scholar
• Zhang HY, Zhang Q, Zhang X, et al. Cancer-related inflammation and Barrett’s carcinogenesis: interleukin-6 and STAT3 mediate apoptotic resistance in transformed Barrett’s cells. Am J Physiol Gastrointest Liver Physiol. 2011;300(3):G454–60. doi:10.1152/ajpgi.00458.201021148399
   PubMed Web of Science ®Google Scholar
• Yu C, Zhang Q, Zhang HY, et al. Targeting the intrinsic inflammatory pathway: honokiol exerts proapoptotic effects through STAT3 inhibition in transformed Barrett’s cells. Am J Physiol Gastrointest Liver Physiol. 2012;303(5):G561–9. doi:10.1152/ajpgi.00033.201222744336
   PubMed Web of Science ®Google Scholar
• Park HS, Park JY, Yu R. Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-alpha and IL-6. Diabetes Res Clin Pract. 2005;69(1):29–35. doi:10.1016/j.diabres.2004.11.00715955385
   PubMed Web of Science ®Google Scholar
• Chemnitzer O, Götzel K, Maurer L, et al. Response to TNF-α is increasing along with the progression in Barrett’s esophagus. Dig Dis Sci. 2017;62(12):3391–3401. doi:10.1007/s10620-017-4821-629086334
   PubMed Web of Science ®Google Scholar
• O’Sullivan KE, Phelan JJ, O’Hanlon C, Lysaght J, O’Sullivan JN, Reynolds JV. The role of inflammation in cancer of the esophagus. Expert Rev Gastroenterol Hepatol. 2014;8(7):749–760. doi:10.1586/17474124.2014.91347824857183
   PubMed Web of Science ®Google Scholar
• Tselepis C, Perry I, Dawson C, et al. Tumour necrosis factor-alpha in Barrett’s oesophagus: a potential novel mechanism of action. Oncogene. 2002;21(39):6071–6081. doi:10.1038/sj.onc.120573112203119
   PubMed Web of Science ®Google Scholar
• Sen M, Hahn F, Black TA, et al. Flow based single cell analysis of the immune landscape distinguishes Barrett’s esophagus from adjacent normal tissue. Oncotarget. 2019;10(38):3592–3604. doi:10.18632/oncotarget.2691131217895
   PubMedGoogle Scholar
• Kavanagh ME, Conroy MJ, Clarke NE, et al. Impact of the inflammatory microenvironment on T-cell phenotype in the progression from reflux oesophagitis to Barrett oesophagus and oesophageal adenocarcinoma. Cancer Lett. 2016;370(1):117–124. doi:10.1016/j.canlet.2015.10.01926519754
   PubMed Web of Science ®Google Scholar
• Lind A, Siersema PD, Kusters JG, Van der Linden JA, Knol EF, Koenderman L. The immune cell composition in Barrett’s metaplastic tissue resembles that in normal duodenal tissue. PLoS One. 2012;7(4):e33899. doi:10.1371/journal.pone.003389922509265
   PubMed Web of Science ®Google Scholar
• Lind A, Siersema PD, Kusters JG, Konijn T, Mebius RE, Koenderman L. The microenvironment in Barrett’s esophagus tissue is characterized by high FOXP3 and RALDH2 levels. Front Immunol. 2018;9:1375. doi:10.3389/fimmu.2018.0137529967615
   PubMed Web of Science ®Google Scholar
• Souza RF. Reflux esophagitis and its role in the pathogenesis of Barrett’s metaplasia. J Gastroenterol. 2017;52(7):767–776. doi:10.1007/s00535-017-1342-128451845
   PubMed Web of Science ®Google Scholar
• Souza RF, Bayeh L, Spechler SJ, Tambar UK, Bruick RK. A new paradigm for GERD pathogenesis. Not acid injury, but cytokine-mediated inflammation driven by HIF-2α: a potential role for targeting HIF-2α to prevent and treat reflux esophagitis. Curr Opin Pharmacol. 2017;37:93–99. doi:10.1016/j.coph.2017.10.00429112883
   PubMed Web of Science ®Google Scholar
• Garalla HM, Lertkowit N, Tiszlavicz L, et al. Matrix metalloproteinase (MMP)-7 in Barrett’s esophagus and esophageal adenocarcinoma: expression, metabolism, and functional significance. Physiol Rep. 2018;6(10):e13683. doi:10.14814/phy2.1368329845775
   PubMed Web of Science ®Google Scholar
• Davelaar AL, Straub D, Buttar NS, Fockens P, Krishnadath KK. Active matrix metalloproteases are expressed early on and are high during the Barrett’s esophagus malignancy sequence. Scand J Gastroenterol. 2015;50(3):321–332. doi:10.3109/00365521.2014.94037925562781
   PubMed Web of Science ®Google Scholar
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   Google Scholar
• Taylor PR, Abnet CC, Dawsey SM. Squamous dysplasia—the precursor lesion for esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 2013;22(4):540–552. doi:10.1158/1055-9965.EPI-12-134723549398
   PubMed Web of Science ®Google Scholar
• Auld M, Srinath H, Jeyarajan E. Oesophageal squamous dysplasia. J Gastrointest Cancer. 2018;49(3):385–388. doi:10.1007/s12029-018-0122-329806061
   PubMed Web of Science ®Google Scholar
• de Andrade Barreto E, de Souza Santos PT, Bergmann A, et al. Alterations in glucose metabolism proteins responsible for the Warburg effect in esophageal squamous cell carcinoma. Exp Mol Pathol. 2016;101(1):66–73. doi:10.1016/j.yexmp.2016.05.01427260309
   PubMed Web of Science ®Google Scholar
• Punnia-Moorthy A. Evaluation of pH changes in inflammation of the subcutaneous air pouch lining in the rat, induced by carrageenan, dextran and Staphylococcus aureus. J Oral Pathol. 1987;16(1):36–44. doi:10.1111/j.1600-0714.1987.tb00674.x2435877
   PubMedGoogle Scholar
• Boedtkjer E, Pedersen SF. The acidic tumor microenvironment as a driver of cancer. Annu Rev Physiol. 2020;82(1):103–126. doi:10.1146/annurev-physiol-021119-03462731730395
   PubMedGoogle Scholar
• Pedersen SF, Novak I, Alves F, Schwab A, Pardo LA. Alternating pH landscapes shape epithelial cancer initiation and progression: focus on pancreatic cancer. Bioessays. 2017;39(6).
   Web of Science ®Google Scholar
• Masoud GN, Li W. HIF-1α pathway: role, regulation and intervention for cancer therapy. Acta Pharm Sin B. 2015;5(5):378–389. doi:10.1016/j.apsb.2015.05.00726579469
   PubMed Web of Science ®Google Scholar
• Sormendi S, Wielockx B. Hypoxia pathway proteins as central mediators of metabolism in the tumor cells and their microenvironment. Front Immunol. 2018;9:40. doi:10.3389/fimmu.2018.0004029434587
   PubMed Web of Science ®Google Scholar
• Kato Y, Maeda T, Suzuki A, Baba Y. Cancer metabolism: new insights into classic characteristics. Jpn Dent Sci Rev. 2018;54(1):8–21. doi:10.1016/j.jdsr.2017.08.00329628997
   PubMed Web of Science ®Google Scholar
• Marín-Hernández A, Gallardo-Pérez JC, Ralph SJ, Rodríguez-Enríquez S, Moreno-Sánchez R. HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms. Mini Rev Med Chem. 2009;9(9):1084–1101. doi:10.2174/13895570978892261019689405
   PubMed Web of Science ®Google Scholar
• Xiaoyu H, Yiru Y, Shuisheng S, et al. The mTOR pathway regulates PKM2 to affect glycolysis in esophageal squamous cell carcinoma. Technol Cancer Res Treat. 2018;17:1533033818780063. doi:10.1177/153303381878006329916308
   PubMed Web of Science ®Google Scholar
• Zeng L, Zhou HY, Tang NN, et al. Wortmannin influences hypoxia-inducible factor-1 alpha expression and glycolysis in esophageal carcinoma cells. World J Gastroenterol. 2016;22(20):4868–4880. doi:10.3748/wjg.v22.i20.486827239113
   PubMed Web of Science ®Google Scholar
• Kolosenko I, Avnet S, Baldini N, Viklund J, De Milito A. Therapeutic implications of tumor interstitial acidification. Semin Cancer Biol. 2017;43:119–133. doi:10.1016/j.semcancer.2017.01.00828188829
   PubMed Web of Science ®Google Scholar
• Drenckhan A, Freytag M, Supuran CT, Sauter G, Izbicki JR, Gros SJ. CAIX furthers tumour progression in the hypoxic tumour microenvironment of esophageal carcinoma and is a possible therapeutic target. J Enzyme Inhib Med Chem. 2018;33(1):1024–1033. doi:10.1080/14756366.2018.147536929865880
   PubMed Web of Science ®Google Scholar
• Jomrich G, Jesch B, Birner P, et al. Stromal expression of carbonic anhydrase IX in esophageal cancer. Clin Transl Oncol. 2014;16(11):966–972. doi:10.1007/s12094-014-1180-z24737069
   PubMed Web of Science ®Google Scholar
• Driessen A, Landuyt W, Pastorekova S, et al. Expression of carbonic anhydrase IX (CA IX), a hypoxia-related protein, rather than vascular-endothelial growth factor (VEGF), a pro-angiogenic factor, correlates with an extremely poor prognosis in esophageal and gastric adenocarcinomas. Ann Surg. 2006;243(3):334–340. doi:10.1097/01.sla.0000201452.09591.f316495697
   PubMed Web of Science ®Google Scholar
• Son SW, Chau GC, Kim ST, Um SH. Vacuolar H+-ATPase subunit V0C regulates aerobic glycolysis of esophageal cancer cells via pkm2 signaling. Cells. 2019;8(10):1137.
   PubMed Web of Science ®Google Scholar
• Li Y, Fu L, Li JB, et al. Increased expression of EIF5A2, via hypoxia or gene amplification, contributes to metastasis and angiogenesis of esophageal squamous cell carcinoma. Gastroenterology. 2014;146(7):1701–13.e9. doi:10.1053/j.gastro.2014.02.02924561231
   PubMed Web of Science ®Google Scholar
• Ahluwalia A, Tarnawski AS. Critical role of hypoxia sensor – HIF-1 in VEGF gene activation. Implications for angiogenesis and tissue injury healing. Curr Med Chem. 2012;19(1):90–97. doi:10.2174/09298671280341394422300081
   PubMed Web of Science ®Google Scholar
• Matsuyama T, Nakanishi K, Hayashi T, et al. Expression of hypoxia‐inducible factor‐1α in esophageal squamous cell carcinoma. Cancer Sci. 2005;96(3):176–182. doi:10.1111/j.1349-7006.2005.00025.x15771621
   PubMed Web of Science ®Google Scholar
• Takala H, Saarnio J, Wiik H, Ohtonen P, Soini Y. HIF-1a and VEGF are associated with disease progression in esophageal carcinoma. J Surg Res. 2011;167(1):41–48. doi:10.1016/j.jss.2009.11.72520451923
   PubMed Web of Science ®Google Scholar
• Tzao C, Lee SC, Tung HJ, et al. Expression of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF)-D as outcome predictors in resected esophageal squamous cell carcinoma. Dis Markers. 2008;25(3):141–148. doi:10.1155/2008/46832319096126
   PubMed Web of Science ®Google Scholar
• Hu X, Lin J, Jiang M, et al. HIF-1α promotes the metastasis of esophageal squamous cell carcinoma by targeting SP1. J Cancer. 2020;11(1):229–240. doi:10.7150/jca.3553731892989
   PubMed Web of Science ®Google Scholar
• Natsuizaka M, Kinugasa H, Kagawa S, et al. IGFBP3 promotes esophageal cancer growth by suppressing oxidative stress in hypoxic tumor microenvironment. Am J Cancer Res. 2014;4(1):29–41.24482736
   PubMed Web of Science ®Google Scholar
• Wu X, Qiao B, Liu Q, Zhang W. Upregulation of extracellular matrix metalloproteinase inducer promotes hypoxia-induced epithelial-mesenchymal transition in esophageal cancer. Mol Med Rep. 2015;12(5):7419–7424. doi:10.3892/mmr.2015.441026458866
   PubMed Web of Science ®Google Scholar
• Jing SW, Wang YD, Kuroda M, et al. HIF-1α contributes to hypoxia-induced invasion and metastasis of esophageal carcinoma via inhibiting E-cadherin and promoting MMP-2 expression. Acta Med Okayama. 2012;66(5):399–407. doi:10.18926/AMO/4896423093058
   PubMed Web of Science ®Google Scholar
• Shen H, Yang Y, Xia S, Rao B, Zhang J, Wang J. Blockage of Nrf2 suppresses the migration and invasion of esophageal squamous cell carcinoma cells in hypoxic microenvironment. Dis Esophagus. 2014;27(7):685–692. doi:10.1111/dote.1212424028437
   PubMed Web of Science ®Google Scholar
• Ping W, Sun W, Zu Y, Chen W, Fu X. Clinicopathological and prognostic significance of hypoxia-inducible factor-1α in esophageal squamous cell carcinoma: a meta-analysis. Tumour Biol. 2014;35(5):4401–4409. doi:10.1007/s13277-013-1579-024425106
   PubMedGoogle Scholar
• Jing SW, Wang J, Xu Q. Expression of hypoxia inducible factor 1 alpha and its clinical significance in esophageal carcinoma: a meta-analysis. Tumour Biol. 2017;39(7):1010428317717983. doi:10.1177/101042831771798328671053
   PubMedGoogle Scholar
• Goscinski MA, Nesland JM, Giercksky KE, Dhakal HP. Primary tumor vascularity in esophagus cancer. CD34 and HIF1-α expression correlate with tumor progression. Histol Histopathol. 2013;28(10):1361–1368. doi:10.14670/HH-28.136123653235
   PubMed Web of Science ®Google Scholar
• Shao C, Yang F, Miao S, et al. Role of hypoxia-induced exosomes in tumor biology. Mol Cancer. 2018;17(1):120. doi:10.1186/s12943-018-0869-y30098600
   PubMedGoogle Scholar
• Chen F, Chu L, Li J, et al. Hypoxia induced changes in miRNAs and their target mRNAs in extracellular vesicles of esophageal squamous cancer cells. Thorac Cancer. 2020;11(3):570–580. doi:10.1111/1759-7714.1329531922357
   PubMed Web of Science ®Google Scholar
• Toschi A, Edelstein J, Rockwell P, Ohh M, Foster DA. HIF alpha expression in VHL-deficient renal cancer cells is dependent on phospholipase D. Oncogene. 2008;27(19):2746–2753. doi:10.1038/sj.onc.121092717998935
   PubMed Web of Science ®Google Scholar
• Toschi A, Lee E, Thompson S, et al. Phospholipase D-mTOR requirement for the Warburg effect in human cancer cells. Cancer Lett. 2010;299(1):72–79. doi:10.1016/j.canlet.2010.08.00620805015
   PubMed Web of Science ®Google Scholar
• Zheng Y, Rodrik V, Toschi A, et al. Phospholipase D couples survival and migration signals in stress response of human cancer cells. J Biol Chem. 2006;281(23):15862–15868. doi:10.1074/jbc.M60066020016595654
   PubMed Web of Science ®Google Scholar
• Mao Y, Wang Y, Dong L, et al. Hypoxic exosomes facilitate angiogenesis and metastasis in esophageal squamous cell carcinoma through altering the phenotype and transcriptome of endothelial cells. J Exp Clin Cancer Res. 2019;38(1):389. doi:10.1186/s13046-019-1384-831488217
   PubMed Web of Science ®Google Scholar
• Li B, Song T-N, Wang F-R, et al. Tumor-derived exosomal HMGB1 promotes esophageal squamous cell carcinoma progression through inducing PD1+ TAM expansion. Oncogenesis. 2019;8(3):17. doi:10.1038/s41389-019-0126-230796203
   PubMedGoogle Scholar
• Yang YC, Liu GJ, Yuan DF, Li CQ, Xue M, Chen LJ. Influence of exosome-derived miR-21 on chemotherapy resistance of esophageal cancer. Eur Rev Med Pharmacol Sci. 2019;23(4):1513–1519. doi:10.26355/eurrev_201902_1710930840273
   PubMed Web of Science ®Google Scholar
• Liao J, Liu R, Shi YJ, Yin LH, Pu YP. Exosome-shuttling microRNA-21 promotes cell migration and invasion-targeting PDCD4 in esophageal cancer. Int J Oncol. 2016;48(6):2567–2579. doi:10.3892/ijo.2016.345327035745
   PubMed Web of Science ®Google Scholar
• Tanaka Y, Kamohara H, Kinoshita K, et al. Clinical impact of serum exosomal microRNA-21 as a clinical biomarker in human esophageal squamous cell carcinoma. Cancer. 2013;119(6):1159–1167. doi:10.1002/cncr.2789523224754
   PubMed Web of Science ®Google Scholar
• Chen Z, Liu Y, Qi B, et al. MicroRNA‑212 facilitates the motility and invasiveness of esophageal squamous carcinoma cells. Mol Med Rep. 2019;20(4):3633–3641. doi:10.3892/mmr.2019.1064731485658
   PubMed Web of Science ®Google Scholar
• Su LL, Chang XJ, Zhou HD, Hou LB, Xue XY. Exosomes in esophageal cancer: a review on tumorigenesis, diagnosis and therapeutic potential. World J Clin Cases. 2019;7(8):908–916. doi:10.12998/wjcc.v7.i8.90831119136
   PubMed Web of Science ®Google Scholar
• Lin M, Zhou C, He S, et al. The research advances of exosomes in esophageal cancer. Biomark Med. 2019;13(8):685–695. doi:10.2217/bmm-2018-031431161775
   PubMed Web of Science ®Google Scholar
• Chen Y, Liu L, Li J, Du Y, Wang J, Liu J. Effects of long noncoding RNA (linc-VLDLR) existing in extracellular vesicles on the occurrence and multidrug resistance of esophageal cancer cells. Pathol Res Pract. 2019;215(3):470–477. doi:10.1016/j.prp.2018.12.03330606658
   PubMed Web of Science ®Google Scholar
• Yu T, Tang B, Sun X. Development of inhibitors targeting hypoxia-inducible factor 1 and 2 for cancer therapy. Yonsei Med J. 2017;58(3):489–496. doi:10.3349/ymj.2017.58.3.48928332352
   PubMed Web of Science ®Google Scholar
• Roma-Rodrigues C, Mendes R, Baptista PV, Fernandes AR. Targeting tumor microenvironment for cancer therapy. Int J Mol Sci. 2019;20(4):840. doi:10.3390/ijms20040840
   PubMed Web of Science ®Google Scholar
• Zhu Y, Zang Y, Zhao F, et al. Inhibition of HIF-1α by PX-478 suppresses tumor growth of esophageal squamous cell cancer in vitro and in vivo. Am J Cancer Res. 2017;7(5):1198–1212.28560067
   PubMed Web of Science ®Google Scholar
• Veglia F, Perego M, Gabrilovich D. Myeloid-derived suppressor cells coming of age. Nat Immunol. 2018;19(2):108–119. doi:10.1038/s41590-017-0022-x29348500
   PubMed Web of Science ®Google Scholar
• Chen M-F, Kuan F-C, Yen T-C, et al. IL-6-stimulated CD11b+ CD14+ HLA-DR− myeloid-derived suppressor cells, are associated with progression and poor prognosis in squamous cell carcinoma of the esophagus. Oncotarget. 2014;5(18):8716–8728. doi:10.18632/oncotarget.236825238263
   PubMedGoogle Scholar
• Gabrilovich DI. MDSC. Cancer Immunol Res. 2017;5(1):3–8. doi:10.1158/2326-6066.CIR-16-029728052991
   PubMed Web of Science ®Google Scholar
• Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9(3):162–174. doi:10.1038/nri250619197294
   PubMed Web of Science ®Google Scholar
• Mazzoni A, Bronte V, Visintin A, et al. Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism. J Immunol. 2002;168(2):689–695. doi:10.4049/jimmunol.168.2.68911777962
   PubMed Web of Science ®Google Scholar
• Liu C, Yu S, Kappes J, et al. Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor-bearing host. Blood. 2007;109(10):4336–4342. doi:10.1182/blood-2006-09-04620117244679
   PubMed Web of Science ®Google Scholar
• Serafini P, Mgebroff S, Noonan K, Borrello I. Myeloid derived suppressor cells promote cross-tolerance in B cell lymphoma by expanding regulatory T cells. Cancer Res. 2008;68(13):5439–5449. doi:10.1158/0008-5472.CAN-07-662118593947
   PubMed Web of Science ®Google Scholar
• Zhou J, Nefedova Y, Lei A, Gabrilovich D. Neutrophils and PMN-MDSC: their biological role and interaction with stromal cells. Semin Immunol. 2018;35:19–28. doi:10.1016/j.smim.2017.12.00429254756
   PubMed Web of Science ®Google Scholar
• Karakasheva TA, Dominguez GA, Hashimoto A, et al. CD38+ M-MDSC expansion characterizes a subset of advanced colorectal cancer patients. JCI Insight. 2018;3(6):e97022. doi:10.1172/jci.insight.97022
   PubMed Web of Science ®Google Scholar
• Gabitass RF, Annels NE, Stocken DD, Pandha HA, Middleton GW. Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13. Cancer Immunol Immunother. 2011;60(10):1419–1430. doi:10.1007/s00262-011-1028-021644036
   PubMed Web of Science ®Google Scholar
• Li P, Chen X, Qin G, et al. Maelstrom directs myeloid-derived suppressor cells to promote esophageal squamous cell carcinoma progression via activation of the Akt1/RelA/IL8 signaling pathway. Cancer Immunol Res. 2018;6(10):1246–1259. doi:10.1158/2326-6066.CIR-17-041530082413
   PubMed Web of Science ®Google Scholar
• Li J, Zhang B-Z, Qin Y-R, et al. CD68 and interleukin 13, prospective immune markers for esophageal squamous cell carcinoma prognosis prediction. Oncotarget. 2016;7(13):15525–15538. doi:10.18632/oncotarget.690026771842
   PubMedGoogle Scholar
• Karakasheva TA, Waldron TJ, Eruslanov E, et al. CD38-expressing myeloid-derived suppressor cells promote tumor growth in a murine model of esophageal cancer. Cancer Res. 2015;75(19):4074–4085. doi:10.1158/0008-5472.CAN-14-363926294209
   PubMed Web of Science ®Google Scholar
• Touzeau C, Moreau P. Daratumumab for the treatment of multiple myeloma. Expert Opin Biol Ther. 2017;17(7):887–893. doi:10.1080/14712598.2017.132257828434255
   PubMed Web of Science ®Google Scholar
• Van Dyken SJ, Locksley RM. Interleukin-4- and interleukin-13-mediated alternatively activated macrophages: roles in homeostasis and disease. Annu Rev Immunol. 2013;31(1):317–343. doi:10.1146/annurev-immunol-032712-09590623298208
   PubMed Web of Science ®Google Scholar
• Gao J, Wu Y, Su Z, et al. Infiltration of alternatively activated macrophages in cancer tissue is associated with MDSC and Th2 polarization in patients with esophageal cancer. PLoS One. 2014;9(8):e104453–e. doi:10.1371/journal.pone.010445325144454
   PubMed Web of Science ®Google Scholar
• Sun -M-M, He -L-L, Zhang H-X, et al. The synergistic effect of esophageal squamous cell carcinoma KYSE150 cells and M2 macrophages on lymphatic endothelial cells. Am J Transl Res. 2017;9(11):5105–5115.29218108
   PubMed Web of Science ®Google Scholar
• Wang P, Xu L-J, Qin -J-J, Zhang L, Zhuang G-H. MicroRNA-155 inversely correlates with esophageal cancer progression through regulating tumor-associated macrophage FGF2 expression. Biochem Biophys Res Commun. 2018;503(2):452–458. doi:10.1016/j.bbrc.2018.04.09429660336
   PubMed Web of Science ®Google Scholar
• Li J, Xie Y, Wang X, et al. Prognostic impact of tumor-associated macrophage infiltration in esophageal cancer: a meta-analysis. Future Oncol. 2019;15(19):2303–2317. doi:10.2217/fon-2018-066931237146
   PubMed Web of Science ®Google Scholar
• Miyashita T, Tajima H, Shah FA, et al. Impact of inflammation–metaplasia–adenocarcinoma sequence and inflammatory microenvironment in esophageal carcinogenesis using surgical rat models. Ann Surg Oncol. 2014;21(6):2012–2019. doi:10.1245/s10434-014-3537-524526548
   PubMed Web of Science ®Google Scholar
• Okamoto M, Koma Y-I, Kodama T, Nishio M, Shigeoka M, Yokozaki H. Growth differentiation factor 15 promotes progression of esophageal squamous cell carcinoma via TGF-β type II receptor activation. Pathobiology. 2020;87(2):1–14.
   Web of Science ®Google Scholar
• Urakawa N, Utsunomiya S, Nishio M, et al. GDF15 derived from both tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression via Akt and Erk pathways. Lab Invest. 2015;95(5):491–503. doi:10.1038/labinvest.2015.3625730371
   PubMed Web of Science ®Google Scholar
• Hosono M, Koma Y-I, Takase N, et al. CXCL8 derived from tumor-associated macrophages and esophageal squamous cell carcinomas contributes to tumor progression by promoting migration and invasion of cancer cells. Oncotarget. 2017;8(62):106071–106088. doi:10.18632/oncotarget.2252629285315
   PubMedGoogle Scholar
• Shigeoka M, Urakawa N, Nakamura T, et al. Tumor associated macrophage expressing CD204 is associated with tumor aggressiveness of esophageal squamous cell carcinoma. Cancer Sci. 2013;104(8):1112–1119. doi:10.1111/cas.1218823648122
   PubMed Web of Science ®Google Scholar
• Chen Y, Du X-Y. Functional properties and intracellular signaling of CCN1/Cyr61. J Cell Biochem. 2007;100(6):1337–1345. doi:10.1002/jcb.2119417171641
   PubMed Web of Science ®Google Scholar
• Shigeoka M, Urakawa N, Nishio M, et al. Cyr61 promotes CD204 expression and the migration of macrophages via MEK/ERK pathway in esophageal squamous cell carcinoma. Cancer Med. 2015;4(3):437–446. doi:10.1002/cam4.40125620088
   PubMed Web of Science ®Google Scholar
• Kodaira H, Koma Y-I, Hosono M, et al. ANXA10 induction by interaction with tumor-associated macrophages promotes the growth of esophageal squamous cell carcinoma. Pathol Int. 2019;69(3):135–147. doi:10.1111/pin.1277130758105
   PubMed Web of Science ®Google Scholar
• Hung M-S, Chen Y-C, Lin P, et al. Cul4A modulates invasion and metastasis of lung cancer through regulation of ANXA10. Cancers (Basel). 2019;11(5):618. doi:10.3390/cancers11050618
   PubMed Web of Science ®Google Scholar
• Wang J, Zhao S, Wang F, Wang J, Zhang Y. Prognostic significance of increased expression of annexin A10 (ANXA10) in serous epithelial ovarian cancer. Med Sci Monit. 2019;25:5666–5673. doi:10.12659/MSM.91591131363077
   PubMed Web of Science ®Google Scholar
• Miyazawa Y, Sekine Y, Kato H, Furuya Y, Koike H, Suzuki K. Simvastatin up-regulates annexin A10 that can inhibit the proliferation, migration, and invasion in androgen-independent human prostate cancer cells. Prostate. 2017;77(4):337–349. doi:10.1002/pros.2327327862098
   PubMed Web of Science ®Google Scholar
• Yang L, Chang -C-C, Sun Z, et al. GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand. Nat Med. 2017;23(10):1158–1166. doi:10.1038/nm.439428846099
   PubMed Web of Science ®Google Scholar
• Fukai Y, Fukuchi M, Masuda N, et al. Reduced expression of transforming growth factor-beta receptors is an unfavorable prognostic factor in human esophageal squamous cell carcinoma. Int J Cancer. 2003;104(2):161–166. doi:10.1002/ijc.1092912569570
   PubMed Web of Science ®Google Scholar
• Cheng H, Chen C, Liu LU, Zhan NA, Li B. Expression of Smad4, TGF-βRII, and p21waf1 in esophageal squamous cell carcinoma tissue. Oncol Lett. 2015;9(6):2847–2853. doi:10.3892/ol.2015.314626137158
   PubMed Web of Science ®Google Scholar
• Calpe S, Hoefnagel S, Bouchmal S, Del Sancho-Serra C, Straub D, Krishnadath KK. Tumor-associated macrophages as novel targets for immunotherapy in esophageal adenocarcinoma. United European Gastroenterol J. 2017;5(5 Supplement 1):A127–A8.
   Google Scholar
• Yang W, Yu J. Immunologic function of dendritic cells in esophageal cancer. Dig Dis Sci. 2008;53(7):1739–1746. doi:10.1007/s10620-007-0095-818080193
   PubMed Web of Science ®Google Scholar
• Barois N, de Saint-vis B, Lebecque S, Geuze HJ, Kleijmeer MJ. MHC class II compartments in human dendritic cells undergo profound structural changes upon activation. Traffic. 2002;3(12):894–905. doi:10.1034/j.1600-0854.2002.31205.x12453152
   PubMed Web of Science ®Google Scholar
• de Saint-vis B, Vincent J, Vandenabeele S, et al. A novel lysosome-associated membrane glycoprotein, DC-LAMP, induced upon DC maturation, is transiently expressed in MHC class II compartment. Immunity. 1998;9(3):325–336. doi:10.1016/S1074-7613(00)80615-99768752
   PubMed Web of Science ®Google Scholar
• Nishimura J, Tanaka H, Yamakoshi Y, et al. Impact of tumor‑infiltrating LAMP‑3 dendritic cells on the prognosis of esophageal squamous cell carcinoma. Esophagus. 2019;16(4):333–344. doi:10.1007/s10388-019-00669-w30968254
   PubMed Web of Science ®Google Scholar
• Li Y, Du W, Han J, Ge J. LAMP3 promotes the invasion of osteosarcoma cells via SPP1 signaling. Mol Med Rep. 2017;16(5):5947–5953. doi:10.3892/mmr.2017.734928849219
   PubMed Web of Science ®Google Scholar
• Liu S, Yue J, Du W, Han J, Zhang W. LAMP3 plays an oncogenic role in osteosarcoma cells partially by inhibiting TP53. Cell Mol Biol Lett. 2018;23:33. doi:10.1186/s11658-018-0099-830008754
   PubMed Web of Science ®Google Scholar
• Liao X, Chen Y, Liu D, Li F, Li X, Jia W. High expression of LAMP3 is a novel biomarker of poor prognosis in patients with esophageal squamous cell carcinoma. Int J Mol Sci. 2015;16(8):17655–17667. doi:10.3390/ijms16081765526263981
   PubMed Web of Science ®Google Scholar
• Lu J, Ma H, Lian S, et al. Clinical significance and prognostic value of the expression of LAMP3 in oral squamous cell carcinoma. Dis Markers. 2017;2017:1218254. doi:10.1155/2017/121825428607528
   PubMed Web of Science ®Google Scholar
• Wculek SK, Cueto FJ, Mujal AM, Melero I, Krummel MF, Sancho D. Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol. 2020;20(1):7–24. doi:10.1038/s41577-019-0210-z31467405
   PubMed Web of Science ®Google Scholar
• Cheever MA, Higano CS. PROVENGE (Sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine. Clin Cancer Res. 2011;17(11):3520–3526. doi:10.1158/1078-0432.CCR-10-312621471425
   PubMed Web of Science ®Google Scholar
• Milano F, Krishnadath KK. Novel therapeutic strategies for treating esophageal adenocarcinoma: the potential of dendritic cell immunotherapy and combinatorial regimens. Hum Immunol. 2008;69(10):614–624. doi:10.1016/j.humimm.2008.07.00618703104
   PubMed Web of Science ®Google Scholar
• Guo G-H, Chen S-Z, Yu J, et al. In vivo anti-tumor effect of hybrid vaccine of dendritic cells and esophageal carcinoma cells on esophageal carcinoma cell line 109 in mice with severe combined immune deficiency. World J Gastroenterol. 2008;14(8):1167–1174. doi:10.3748/wjg.14.116718300341
   PubMed Web of Science ®Google Scholar
• Milano F, Rygiel AM, Buttar N, et al. An ex vivo readout for evaluation of dendritic cell-induced autologous cytotoxic T lymphocyte responses against esophageal cancer. Cancer Immunol Immunother. 2007;56(12):1967–1977. doi:10.1007/s00262-007-0341-017564704
   PubMed Web of Science ®Google Scholar
• Narita M, Kanda T, Abe T, et al. Immune responses in patients with esophageal cancer treated with SART1 peptide‑pulsed dendritic cell vaccine. Int J Oncol. 2015;46(4):1699–1709. doi:10.3892/ijo.2015.284625625346
   PubMed Web of Science ®Google Scholar
• Wang C, Pu J, Yu H, et al. A dendritic cell vaccine combined with radiotherapy activates the specific immune response in patients with esophageal cancer. J Immunother. 2017;40(2):71–76. doi:10.1097/CJI.000000000000015528125513
   PubMed Web of Science ®Google Scholar
• Jiang D, Liu Y, Wang H, et al. Tumour infiltrating lymphocytes correlate with improved survival in patients with esophageal squamous cell carcinoma. Sci Rep. 2017;7:44823. doi:10.1038/srep4482328322245
   PubMed Web of Science ®Google Scholar
• Sudo T, Nishida R, Kawahara A, et al. Clinical impact of tumor-infiltrating lymphocytes in esophageal squamous cell carcinoma. Ann Surg Oncol. 2017;24(12):3763–3770. doi:10.1245/s10434-017-5796-428160141
   PubMed Web of Science ®Google Scholar
• Svensson MC, Warfvinge CF, Fristedt R, et al. The integrative clinical impact of tumor-infiltrating T lymphocytes and NK cells in relation to B lymphocyte and plasma cell density in esophageal and gastric adenocarcinoma. Oncotarget. 2017;8(42):72108–72126. doi:10.18632/oncotarget.1943729069772
   PubMedGoogle Scholar
• Yagi T, Baba Y, Ishimoto T, et al. PD-L1 expression, tumor-infiltrating lymphocytes, and clinical outcome in patients with surgically resected esophageal cancer. Ann Surg. 2019;269(3):471–478. doi:10.1097/SLA.000000000000261629206673
   PubMed Web of Science ®Google Scholar
• Lee N, Zakka LR, Mihm MC Jr., Schatton T. Tumour-infiltrating lymphocytes in melanoma prognosis and cancer immunotherapy. Pathology. 2016;48(2):177–187. doi:10.1016/j.pathol.2015.12.00627020390
   PubMed Web of Science ®Google Scholar
• Stanton SE, Disis ML. Clinical significance of tumor-infiltrating lymphocytes in breast cancer. J Immunother Cancer. 2016;4:59. doi:10.1186/s40425-016-0165-627777769
   PubMed Web of Science ®Google Scholar
• Zhang D, He W, Wu C, et al. Scoring system for tumor-infiltrating lymphocytes and its prognostic value for gastric cancer. Front Immunol. 2019;10:71. doi:10.3389/fimmu.2019.0007130761139
   PubMed Web of Science ®Google Scholar
• Zhu Y, Li M, Mu D, et al. CD8+/FOXP3+ ratio and PD-L1 expression associated with survival in pT3N0M0 stage esophageal squamous cell cancer. Oncotarget. 2016;7(44):71455–71465. doi:10.18632/oncotarget.1221327683115
   PubMedGoogle Scholar
• Rauser S, Langer R, Tschernitz S, et al. High number of CD45RO+ tumor infiltrating lymphocytes is an independent prognostic factor in non-metastasized (stage I-IIA) esophageal adenocarcinoma. BMC Cancer. 2010;10(1):608. doi:10.1186/1471-2407-10-60821054833
   PubMedGoogle Scholar
• Zhang G, Liu W-L, Zhang L, et al. Involvement of indoleamine 2,3-dioxygenase in impairing tumor-infiltrating CD8+ T-cell functions in esophageal squamous cell carcinoma. Clin Dev Immunol. 2011;2011:384726. doi:10.1155/2011/38472622013481
   PubMedGoogle Scholar
• Kiyozumi Y, Baba Y, Okadome K, et al. IDO1 expression is associated with immune tolerance and poor prognosis in patients with surgically resected esophageal cancer. Ann Surg. 2019;269(6):1101–1108. doi:10.1097/SLA.000000000000275431082908
   PubMed Web of Science ®Google Scholar
• Sucher R, Kurz K, Weiss G, Margreiter R, Fuchs D, Brandacher G. IDO-mediated tryptophan degradation in the pathogenesis of malignant tumor disease. Int J Tryptophan Res. 2010;3:113–120. doi:10.4137/IJTR.S415722084593
   PubMedGoogle Scholar
• Cui G, Li C, Xu G, et al. Tumor-associated fibroblasts and microvessels contribute to the expression of immunosuppressive factor indoleamine 2, 3-dioxygenase in human esophageal cancers. Pathol Oncol Res. 2018;24(2):269–275. doi:10.1007/s12253-017-0244-028470572
   PubMed Web of Science ®Google Scholar
• Chen L, Han X. Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. J Clin Invest. 2015;125(9):3384–3391. doi:10.1172/JCI8001126325035
   PubMed Web of Science ®Google Scholar
• Wang Q, Feng F, Wang F, et al. PD-L1 expression on tumor cells was associated with unfavorable prognosis in esophageal squamous cell carcinoma. J Cancer. 2018;9(12):2224–2231. doi:10.7150/jca.2449329937943
   PubMed Web of Science ®Google Scholar
• Hsieh -C-C, Hsu H-S, Li AF-Y, Chen Y-J. Clinical relevance of PD-L1 and PD-L2 overexpression in patients with esophageal squamous cell carcinoma. J Thorac Dis. 2018;10(7):4433–4444. doi:10.21037/jtd.2018.06.16730174892
   PubMed Web of Science ®Google Scholar
• Jiang Y, Lo AWI, Wong A, et al. Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma. Oncotarget. 2017;8(18):30175–30189. doi:10.18632/oncotarget.1562128404915
   PubMedGoogle Scholar
• Guo W, Wang P, Li N, et al. Prognostic value of PD-L1 in esophageal squamous cell carcinoma: a meta-analysis. Oncotarget. 2017;9(17):13920–13933. doi:10.18632/oncotarget.2381029568405
   PubMedGoogle Scholar
• Kollmann D, Ignatova D, Jedamzik J, et al. PD-L1 expression is an independent predictor of favorable outcome in patients with localized esophageal adenocarcinoma. Oncoimmunology. 2018;7(6):e1435226. doi:10.1080/2162402X.2018.143522629872575
   PubMed Web of Science ®Google Scholar
• Metges J, François E, Shah M, et al. The Phase 3 KEYNOTE-181 study: pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer. Ann Oncol. 2019;30(Suppl 4):iv130–iv. doi:10.1093/annonc/mdz154.011
   Google Scholar
• Shah MA, Kojima T, Hochhauser D, et al. Efficacy and safety of pembrolizumab for heavily pretreated patients with advanced, metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: the phase 2 KEYNOTE-180 study. JAMA Oncol. 2019;5(4):546–550. doi:10.1001/jamaoncol.2018.544130570649
   PubMed Web of Science ®Google Scholar
• Kuo H-Y, Guo J-C, Hsu C-H. Anti-PD-1 immunotherapy in advanced esophageal squamous cell carcinoma: a long-awaited breakthrough finally arrives. J Formos Med Assoc. 2020;119(2):565–568. doi:10.1016/j.jfma.2019.10.01031668650
   PubMed Web of Science ®Google Scholar
• Wang W, Chen D, Zhao Y, et al. Characterization of LAG-3, CTLA-4, and CD8+ TIL density and their joint influence on the prognosis of patients with esophageal squamous cell carcinoma. Ann Transl Med. 2019;7(23):776. doi:10.21037/atm.2019.11.3832042792
   PubMed Web of Science ®Google Scholar
• Wang S, Li Z, Hu G. Prognostic role of intratumoral, zhi’an li2 and guoming hu3 IL-17A expression by immunohistochemistry in solid tumors: a meta-analysis. Oncotarget. 2017;8(39):66382–66391. doi:10.18632/oncotarget.1880729029520
   PubMedGoogle Scholar
• Lu L, Pan K, Zheng H-X, et al. IL-17A promotes immune cell recruitment in human esophageal cancers and the infiltrating dendritic cells represent a positive prognostic marker for patient survival. J Immunother. 2013;36(8):451–458. doi:10.1097/CJI.0b013e3182a802cf23994890
   PubMed Web of Science ®Google Scholar
• Lu L, Weng C, Mao H, et al. IL-17A promotes migration and tumor killing capability of B cells in esophageal squamous cell carcinoma. Oncotarget. 2016;7(16):21853–21864. doi:10.18632/oncotarget.786926942702
   PubMedGoogle Scholar
• Chen D, Jiang R, Mao C, et al. Chemokine/chemokine receptor interactions contribute to the accumulation of Th17 cells in patients with esophageal squamous cell carcinoma. Hum Immunol. 2012;73(11):1068–1072. doi:10.1016/j.humimm.2012.07.33322863447
   PubMed Web of Science ®Google Scholar
• Chen D, Hu Q, Mao C, et al. Increased IL-17-producing CD4+ T cells in patients with esophageal cancer. Cell Immunol. 2012;272(2):166–174. doi:10.1016/j.cellimm.2011.10.01522082565
   PubMed Web of Science ®Google Scholar
• Liu D, Zhang R, Wu J, et al. Interleukin-17A promotes esophageal adenocarcinoma cell invasiveness through ROS-dependent, NF-κB-mediated MMP-2/9 activation. Oncol Rep. 2017;37(3):1779–1785. doi:10.3892/or.2017.542628184939
   PubMed Web of Science ®Google Scholar
• Shitara K, Nishikawa H. Regulatory T cells: a potential target in cancer immunotherapy. Ann N Y Acad Sci. 2018;1417(1):104–115. doi:10.1111/nyas.1362529566262
   PubMed Web of Science ®Google Scholar
• Facciabene A, Motz GT, Coukos G. T-regulatory cells: key players in tumor immune escape and angiogenesis. Cancer Res. 2012;72(9):2162–2171. doi:10.1158/0008-5472.CAN-11-368722549946
   PubMed Web of Science ®Google Scholar
• Paluskievicz CM, Cao X, Abdi R, Zheng P, Liu Y, Bromberg JS. T regulatory cells and priming the suppressive tumor microenvironment. Front Immunol. 2019;10:2453. doi:10.3389/fimmu.2019.0245331681327
   PubMed Web of Science ®Google Scholar
• Wang G, Liu G, Liu Y, Li X, Su Z. FOXP3 expression in esophageal cancer cells is associated with poor prognosis in esophageal cancer. Hepatogastroenterology. 2012;59(119):2186–2191. doi:10.5754/hge1196122389297
   PubMedGoogle Scholar
• Huang C, Fu Z-X. Localization of IL-17+Foxp3+ T cells in esophageal cancer. Immunol Invest. 2011;40(4):400–412. doi:10.3109/08820139.2011.55548921314287
   PubMed Web of Science ®Google Scholar
• Karstens K-F, Kempski J, Giannou AD, et al. Anti‑inflammatory microenvironment of esophageal adenocarcinomas negatively impacts survival. Cancer Immunol Immunother. 2020. doi:10.1007/s00262-020-2517-8
   PubMed Web of Science ®Google Scholar
• Xue L, Lu HQ, He J, et al. Expression of FOXP3 in esophageal squamous cell carcinoma relating to the clinical data. Dis Esophagus. 2010;23(4):340–346. doi:10.1111/j.1442-2050.2009.01013.x19788437
   PubMed Web of Science ®Google Scholar
• Yue Y, Lian J, Wang T, et al. Interleukin-33-nuclear factor-κB-CCL2 signaling pathway promotes progression of esophageal squamous cell carcinoma by directing regulatory T cells. Cancer Sci. 2020;111(3):795–806. doi:10.1111/cas.1429331883400
   PubMed Web of Science ®Google Scholar
• Cui G, Li Z, Ren J, Yuan A. IL-33 in the tumor microenvironment is associated with the accumulation of FoxP3-positive regulatory T cells in human esophageal carcinomas. Virchows Arch. 2019;475(5):579–586. doi:10.1007/s00428-019-02579-931062086
   PubMed Web of Science ®Google Scholar
• Tokunaga R, Naseem M, Lo JH, et al. B cell and B cell-related pathways for novel cancer treatments. Cancer Treat Rev. 2019;73:10–19. doi:10.1016/j.ctrv.2018.12.00130551036
   PubMed Web of Science ®Google Scholar
• Qian L, Bian G-R, Zhou Y, et al. Clinical significance of regulatory B cells in the peripheral blood of patients with oesophageal cancer. Cent Eur J Immunol. 2015;40(2):263–265. doi:10.5114/ceji.2015.5284026557042
   PubMed Web of Science ®Google Scholar
• Schwartz M, Zhang Y, Rosenblatt JD. B cell regulation of the anti-tumor response and role in carcinogenesis. J Immunother Cancer. 2016;4(1):40. doi:10.1186/s40425-016-0145-x27437104
   PubMedGoogle Scholar
• Bond DA, Woyach JA. Targeting BTK in CLL: beyond Ibrutinib. Curr Hematol Malig Rep. 2019;14(3):197–205. doi:10.1007/s11899-019-00512-031028669
   PubMed Web of Science ®Google Scholar
• Sagiv-Barfi I, Kohrt HEK, Czerwinski DK, Ng PP, Chang BY, Levy R. Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK. Proc Natl Acad Sci U S A. 2015;112(9):E966–E72. doi:10.1073/pnas.150071211225730880
   PubMed Web of Science ®Google Scholar
• Xu B, Chen L, Li J, et al. Prognostic value of tumor infiltrating NK cells and macrophages in stage II+III esophageal cancer patients. Oncotarget. 2016;7(46):74904–74916. doi:10.18632/oncotarget.1248427736796
   PubMedGoogle Scholar
• Anderson AC, Joller N, Kuchroo VK. Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. Immunity. 2016;44(5):989–1004. doi:10.1016/j.immuni.2016.05.00127192565
   PubMed Web of Science ®Google Scholar
• Zheng Y, Li Y, Lian J, et al. TNF-α-induced Tim-3 expression marks the dysfunction of infiltrating natural killer cells in human esophageal cancer. J Transl Med. 2019;17(1):165. doi:10.1186/s12967-019-1917-031109341
   PubMedGoogle Scholar
• Lim KS, Mimura K, Kua L-F, Shiraishi K, Kono K. Implication of highly cytotoxic natural killer cells for esophageal squamous cell carcinoma treatment. J Immunother. 2018;41(6):261–273. doi:10.1097/CJI.000000000000022729683892
   PubMed Web of Science ®Google Scholar
• Trivanović D, Krstić J, Djordjević IO, et al. The roles of mesenchymal stromal/stem cells in tumor microenvironment associated with inflammation. Mediators Inflamm. 2016;2016:7314016. doi:10.1155/2016/731401627630452
   PubMed Web of Science ®Google Scholar
• Atiya H, Frisbie L, Pressimone C, Coffman L. Mesenchymal stem cells in the tumor microenvironment. Adv Exp Med Biol. 2020;1234:31–42.32040853
   PubMed Web of Science ®Google Scholar
• Rahmatizadeh F, Gholizadeh-Ghaleh Aziz S, Khodadadi K, et al. Bidirectional and opposite effects of naïve mesenchymal stem cells on tumor growth and progression. Adv Pharm Bull. 2019;9(4):539–558. doi:10.15171/apb.2019.06331857958
   PubMed Web of Science ®Google Scholar
• Tian LLH, Yue W, Zhu F, Li S, Li W. Human mesenchymal stem cells play a dual role on tumor cell growth in vitro and in vivo. J Cell Physiol. 2011;226(7):1860–1867. doi:10.1002/jcp.2251121442622
   PubMed Web of Science ®Google Scholar
• Yang X, Li Z, Ma Y, et al. Human umbilical cord mesenchymal stem cells promote carcinoma growth and lymph node metastasis when co-injected with esophageal carcinoma cells in nude mice. Cancer Cell Int. 2014;14(1):93. doi:10.1186/s12935-014-0093-925298750
   PubMedGoogle Scholar
• Liu T, Zhou L, Li D, Andl T, Zhang Y. Cancer-associated fibroblasts build and secure the tumor. Front Cell Dev Biol. 2019;7:60. doi:10.3389/fcell.2019.0006031106200
   PubMed Web of Science ®Google Scholar
• Truffi M, Mazzucchelli S, Bonizzi A, et al. Nano-strategies to target breast cancer-associated fibroblasts: rearranging the tumor microenvironment to achieve antitumor efficacy. Int J Mol Sci. 2019;20(6):1263. doi:10.3390/ijms20061263
   PubMed Web of Science ®Google Scholar
• Pereira BA, Vennin C, Papanicolaou M, et al. CAF subpopulations: a new reservoir of stromal targets in pancreatic cancer. Trends Cancer. 2019;5(11):724–741. doi:10.1016/j.trecan.2019.09.01031735290
   PubMed Web of Science ®Google Scholar
• Marsh T, Pietras K, McAllister SS. Fibroblasts as architects of cancer pathogenesis. Biochim Biophys Acta. 2013;1832(7):1070–1078. doi:10.1016/j.bbadis.2012.10.01323123598
   PubMed Web of Science ®Google Scholar
• Mishra PJ, Mishra PJ, Glod JW, Banerjee D. Mesenchymal stem cells: flip side of the coin. Cancer Res. 2009;69(4):1255–1258. doi:10.1158/0008-5472.CAN-08-356219208837
   PubMed Web of Science ®Google Scholar
• Ha SY, Yeo S-Y, Xuan Y-H, Kim S-H, Hoheisel JD. The prognostic significance of cancer-associated fibroblasts in esophageal squamous cell carcinoma. PLoS One. 2014;9(6):e99955–e. doi:10.1371/journal.pone.009995524945657
   PubMed Web of Science ®Google Scholar
• Cheng Y, Wang K, Ma W, et al. Cancer-associated fibroblasts are associated with poor prognosis in esophageal squamous cell carcinoma after surgery. Int J Clin Exp Med. 2015;8(2):1896–1903.25932118
   PubMed Web of Science ®Google Scholar
• Wang J, Zhang G, Wang J, Wang L, Huang X, Cheng Y. The role of cancer-associated fibroblasts in esophageal cancer. J Transl Med. 2016;14(1):30. doi:10.1186/s12967-016-0788-x26822225
   PubMedGoogle Scholar
• Kashima H, Noma K, Ohara T, et al. Cancer-associated fibroblasts (CAFs) promote the lymph node metastasis of esophageal squamous cell carcinoma. Int J Cancer. 2019;144(4):828–840. doi:10.1002/ijc.3195330367467
   PubMed Web of Science ®Google Scholar
• Yang Z-T, Yeo S-Y, Yin Y-X, et al. Tenascin-C, a prognostic determinant of esophageal squamous cell carcinoma. PLoS One. 2016;11(1):e0145807–e. doi:10.1371/journal.pone.014580726731558
   PubMed Web of Science ®Google Scholar
• Ebbing EA, van der Zalm AP, Steins A, et al. Stromal-derived interleukin 6 drives epithelial-to mesenchymal transition and therapy resistance in esophageal adenocarcinoma. Proc Natl Acad Sci U S A. 2019;116(6):2237–2242. doi:10.1073/pnas.182045911630670657
   PubMed Web of Science ®Google Scholar
• Qiao Y, Zhang C, Li A, et al. IL6 derived from cancer-associated fibroblasts promotes chemoresistance via CXCR7 in esophageal squamous cell carcinoma. Oncogene. 2018;37(7):873–883. doi:10.1038/onc.2017.38729059160
   PubMed Web of Science ®Google Scholar
• Kato T, Noma K, Ohara T, et al. Cancer-associated fibroblasts affect intratumoral CD8þ and FoxP3þ T cells via IL6 in the tumor microenvironment. Clin Cancer Res. 2018;24(19):4820–4833. doi:10.1158/1078-0432.CCR-18-020529921731
   PubMed Web of Science ®Google Scholar
• Higashino N, Koma Y-I, Hosono M, et al. Fibroblast activation protein-positive fibroblasts promote tumor progression through secretion of CCL2 and interleukin-6 in esophageal squamous cell carcinoma. Lab Invest. 2019;99(6):777–792. doi:10.1038/s41374-018-0185-630683902
   PubMed Web of Science ®Google Scholar
• Tian B, Chen X, Zhang H, et al. Urokinase plasminogen activator secreted by cancer-associated fibroblasts induces tumor progression via PI3K/AKT and ERK signaling in esophageal squamous cell carcinoma. Oncotarget. 2017;8(26):42300–42313. doi:10.18632/oncotarget.1585728404945
   PubMedGoogle Scholar
• Yeo S-Y, Ha S-Y, Lee K-W, et al. Twist1 is highly expressed in cancer-associated fibroblasts of esophageal squamous cell carcinoma with a prognostic significance. Oncotarget. 2017;8(39):65265–65280. doi:10.18632/oncotarget.1794129029429
   PubMedGoogle Scholar
• Zhu X, Han S, Wu S, Bai Y, Zhang N, Wei L. Dual role of twist1 in cancer-associated fibroblasts and tumor cells promoted epithelial-mesenchymal transition of esophageal cancer. Exp Cell Res. 2019;375(2):41–50. doi:10.1016/j.yexcr.2019.01.00230611739
   PubMed Web of Science ®Google Scholar
• Grugan KD, Miller CG, Yao Y, et al. Fibroblast-secreted hepatocyte growth factor plays a functional role in esophageal squamous cell carcinoma invasion. Proc Natl Acad Sci U S A. 2010;107(24):11026–11031. doi:10.1073/pnas.091429510720534479
   PubMed Web of Science ®Google Scholar
• Xu Z, Wang S, Wu M, Zeng W, Wang X, Dong Z. TGFβ1 and HGF protein secretion by esophageal squamous epithelial cells and stromal fibroblasts in oesophageal carcinogenesis. Oncol Lett. 2013;6(2):401–406. doi:10.3892/ol.2013.140924137336
   PubMed Web of Science ®Google Scholar
• Ozawa Y, Nakamura Y, Fujishima F, et al. c-Met in esophageal squamous cell carcinoma: an independent prognostic factor and potential therapeutic target. BMC Cancer. 2015;15(1):451. doi:10.1186/s12885-015-1450-326036285
   PubMedGoogle Scholar
• Ren Y, Cao B, Law S, et al. Hepatocyte growth factor promotes cancer cell migration and angiogenic factors expression: a prognostic marker of human esophageal squamous cell carcinomas. Clin Cancer Res. 2005;11(17):6190–6197. doi:10.1158/1078-0432.CCR-04-255316144920
   PubMed Web of Science ®Google Scholar
• Gholamin M, Moaven O, Memar B, et al. Overexpression and interactions of interleukin-10, transforming growth factor beta, and vascular endothelial growth factor in esophageal squamous cell carcinoma. World J Surg. 2009;33(7):1439–1445. doi:10.1007/s00268-009-0070-y19440651
   PubMed Web of Science ®Google Scholar
• Wang H, Jiang D, Song Q, et al. Prognostic impact and potential interaction of EGFR and c-Met in the progression of esophageal squamous cell carcinoma. Tumour Biol. 2016;37(7):9771–9779. doi:10.1007/s13277-015-4692-426810066
   PubMedGoogle Scholar
• De Silva DM, Roy A, Kato T, et al. Targeting the hepatocyte growth factor/Met pathway in cancer. Biochem Soc Trans. 2017;45(4):855–870. doi:10.1042/BST2016013228673936
   PubMedGoogle Scholar
• Cheng F, Guo D. MET in glioma: signaling pathways and targeted therapies. J Exp Clin Cancer Res. 2019;38(1):270. doi:10.1186/s13046-019-1269-x31221203
   PubMedGoogle Scholar
• Mazzocca A, Fransvea E, Lavezzari G, Antonaci S, Giannelli G. Inhibition of transforming growth factor beta receptor I kinase blocks hepatocellular carcinoma growth through neo-angiogenesis regulation. Hepatology. 2009;50(4):1140–1151. doi:10.1002/hep.2311819711426
   PubMed Web of Science ®Google Scholar
• Watanabe S, Noma K, Ohara T, et al. Photoimmunotherapy for cancer-associated fibroblasts targeting fibroblast activation protein in human esophageal squamous cell carcinoma. Cancer Biol Ther. 2019;20(9):1234–1248. doi:10.1080/15384047.2019.161756631185791
   PubMed Web of Science ®Google Scholar
• Mitsunaga M, Ogawa M, Kosaka N, Rosenblum LT, Choyke PL, Kobayashi H. Cancer cell-selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules. Nat Med. 2011;17(12):1685–1691. doi:10.1038/nm.255422057348
   PubMed Web of Science ®Google Scholar
• Palumbo A Jr., Meireles Da Costa N, Pontes B, et al. Esophageal cancer development: crucial clues arising from the extracellular matrix. Cells. 2020;9(2):E455. doi:10.3390/cells902045532079295
   PubMed Web of Science ®Google Scholar
• Najafi M, Mortezaee K, Majidpoor J. Stromal reprogramming: a target for tumor therapy. Life Sci. 2019;239:117049. doi:10.1016/j.lfs.2019.11704931730862
   PubMed Web of Science ®Google Scholar
• Leppänen J, Bogdanoff S, Lehenkari PP, et al. Tenascin-C and fibronectin in normal esophageal mucosa, Barrett’s esophagus, dysplasia and adenocarcinoma. Oncotarget. 2017;8(40):66865–66877. doi:10.18632/oncotarget.1919628978001
   PubMedGoogle Scholar
• Senthebane DA, Jonker T, Rowe A, et al. The role of tumor microenvironment in chemoresistance: 3D extracellular matrices as accomplices. Int J Mol Sci. 2018;19(10):2861. doi:10.3390/ijms19102861
   PubMed Web of Science ®Google Scholar
• Fang M, Yuan J, Peng C, Li Y. Collagen as a double-edged sword in tumor progression. Tumour Biol. 2014;35(4):2871–2882. doi:10.1007/s13277-013-1511-724338768
   PubMedGoogle Scholar
• Paszek MJ, Zahir N, Johnson KR, et al. Tensional homeostasis and the malignant phenotype. Cancer Cell. 2005;8(3):241–254. doi:10.1016/j.ccr.2005.08.01016169468
   PubMed Web of Science ®Google Scholar
• Hanley CJ, Noble F, Ward M, et al. A subset of myofibroblastic cancer-associated fibroblasts regulate collagen fiber elongation, which is prognostic in multiple cancers. Oncotarget. 2016;7(5):6159–6174. doi:10.18632/oncotarget.674026716418
   PubMedGoogle Scholar
• Fang S, Dai Y, Mei Y, et al. Clinical significance and biological role of cancer-derived type I collagen in lung and esophageal cancers. Thorac Cancer. 2019;10(2):277–288. doi:10.1111/1759-7714.1294730604926
   PubMed Web of Science ®Google Scholar
• Xiao J, Yang W, Xu B, et al. Expression of fibronectin in esophageal squamous cell carcinoma and its role in migration. BMC Cancer. 2018;18(1):976. doi:10.1186/s12885-018-4850-330314454
   PubMedGoogle Scholar
• Orend G, Chiquet-Ehrismann R. Adhesion modulation by antiadhesive molecules of the extracellular matrix. Exp Cell Res. 2000;261(1):104–110. doi:10.1006/excr.2000.504111082280
   PubMed Web of Science ®Google Scholar
• Yang Z, Zhang C, Feng Y, Qi W, Cui Y, Xuan Y. Tenascin-C is involved in promotion of cancer stemness via the Akt/HIF1ɑ axis in esophageal squamous cell carcinoma. Exp Mol Pathol. 2019;109:104239. doi:10.1016/j.yexmp.2019.03.00730904401
   PubMed Web of Science ®Google Scholar
• Luo M-L, Zhou Z, Sun L, et al. An ADAM12 and FAK positive feedback loop amplifies the interaction signal of tumor cells with extracellular matrix to promote esophageal cancer metastasis. Cancer Lett. 2018;422:118–128. doi:10.1016/j.canlet.2018.02.03129476791
   PubMed Web of Science ®Google Scholar
• Mäki JM, Tikkanen H, Kivirikko KI. Cloning and characterization of a fifth human lysyl oxidase isoenzyme: the third member of the lysyl oxidase-related subfamily with four scavenger receptor cysteine-rich domains. Matrix Biol. 2001;20(7):493–496. doi:10.1016/S0945-053X(01)00157-311691589
   PubMed Web of Science ®Google Scholar
• Wang SX, Mure M, Medzihradszky KF, et al. A crosslinked cofactor in lysyl oxidase: redox function for amino acid side chains. Science. 1996;273(5278):1078–1084. doi:10.1126/science.273.5278.10788688089
   PubMed Web of Science ®Google Scholar
• Kalikawe R, Baba Y, Nomoto D, et al. Lysyl oxidase impacts disease outcomes and correlates with global DNA hypomethylation in esophageal cancer. Cancer Sci. 2019;110(12):3727–3737. doi:10.1111/cas.1421431599475
   PubMed Web of Science ®Google Scholar
• Sakai M, Kato H, Sano A, et al. Expression of lysyl oxidase is correlated with lymph node metastasis and poor prognosis in esophageal squamous cell carcinoma. Ann Surg Oncol. 2009;16(9):2494–2501. doi:10.1245/s10434-009-0559-519526206
   PubMed Web of Science ®Google Scholar
• Xie W, Huang P, Wu B, et al. Clinical significance of LOXL4 expression and features of LOXL4‑associated protein–protein interaction network in esophageal squamous cell carcinoma. Amino Acids. 2019;51(5):813–828. doi:10.1007/s00726-019-02723-430900087
   PubMed Web of Science ®Google Scholar
• Hoque A, Lippman SM, Wu -T-T, et al. Increased 5-lipoxygenase expression and induction of apoptosis by its inhibitors in esophageal cancer: a potential target for prevention. Carcinogenesis. 2005;26(4):785–791. doi:10.1093/carcin/bgi02615661803
   PubMed Web of Science ®Google Scholar
• Shi H-Y, Lv F-J, Zhu S-T, Wang Q-G, Zhang S-T. Dual inhibition of 5-LOX and COX-2 suppresses esophageal squamous cell carcinoma. Cancer Lett. 2011;309(1):19–26. doi:10.1016/j.canlet.2011.05.01021652147
   PubMed Web of Science ®Google Scholar
• Curran S, Murray GI. Matrix metalloproteinases in tumour invasion and metastasis. J Pathol. 1999;189(3):300–308. doi:10.1002/(SICI)1096-9896(199911)189:3<300::AID-PATH456>3.0.CO;2-C10547590
   PubMed Web of Science ®Google Scholar
• Stamenkovic I. Matrix metalloproteinases in tumor invasion and metastasis. Semin Cancer Biol. 2000;10(6):415–433. doi:10.1006/scbi.2000.037911170864
   PubMed Web of Science ®Google Scholar
• Lu H, Bhat AA, Peng D, et al. APE1 upregulates MMP-14 via redox-sensitive ARF6-mediated recycling to promote cell invasion of esophageal. Cancer Res. 2019;79(17):4426–4438. doi:10.1158/0008-5472.CAN-19-023731308045
   PubMed Web of Science ®Google Scholar
• Carmeliet P. Mechanisms of angiogenesis and arteriogenesis. Nat Med. 2000;6(4):389–395. doi:10.1038/7465110742145
   PubMed Web of Science ®Google Scholar
• Groblewska M, Siewko M, Mroczko B, Szmitkowski M. The role of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the development of esophageal cancer. Folia Histochem Cytobiol. 2012;50(1):12–19. doi:10.5603/FHC.2012.000222532131
   PubMed Web of Science ®Google Scholar
• Li Y, Ma J, Guo Q, et al. Overexpression of MMP-2 and MMP-9 in esophageal squamous cell carcinoma. Dis Esophagus. 2009;22(8):664–667. doi:10.1111/j.1442-2050.2008.00928.x19191857
   PubMed Web of Science ®Google Scholar
• Zhang J, Jin X, Fang S, et al. The functional SNP in the matrix metalloproteinase-3 promoter modifies susceptibility and lymphatic metastasis in esophageal squamous cell carcinoma but not in gastric cardiac adenocarcinoma. Carcinogenesis. 2004;25(12):2519–2524. doi:10.1093/carcin/bgh26915319302
   PubMed Web of Science ®Google Scholar
• Miao S, Zhou S-Y, Han C-S, Zhang L-N, Sun H-B, Yang B. Clinicopathological significance of matrix metalloproteinase-7 protein expression in esophageal cancer: a meta-analysis. Drug Des Devel Ther. 2015;9:3729–3740. doi:10.2147/DDDT.S85987
   PubMed Web of Science ®Google Scholar
• Wu J, Zhang L, Luo H, Zhu Z, Zhang C, Hou Y. Association of matrix metalloproteinases-9 gene polymorphisms with genetic susceptibility to esophageal squamous cell carcinoma. DNA Cell Biol. 2008;27(10):553–557. doi:10.1089/dna.2008.073218680431
   PubMed Web of Science ®Google Scholar
• Han F, Zhang S, Zhang L, Hao Q. The overexpression and predictive significance of MMP-12 in esophageal squamous cell carcinoma. Pathol Res Pract. 2017;213(12):1519–1522. doi:10.1016/j.prp.2017.09.02329033183
   PubMed Web of Science ®Google Scholar
• Chen L, Di D, Luo G, et al. Immunochemical staining of MT2-MMP correlates positively to angiogenesis of human esophageal cancer. Anticancer Res. 2010;30(10):4363–4368.21036765
   PubMed Web of Science ®Google Scholar
• Xue Z, Wu X, Chen X, Luo Q. MT3-MMP down- regulation promotes tumorigenesis and correlates to poor prognosis in esophageal squamous cell carcinoma. Cancer Med. 2016;5(9):2459–2468. doi:10.1002/cam4.79027292876
   PubMed Web of Science ®Google Scholar
• Zhu Y-H, Fu L, Chen L, et al. Downregulation of the novel tumor suppressor DIRAS1 predicts poor prognosis in esophageal squamous cell carcinoma. Cancer Res. 2013;73(7):2298–2309. doi:10.1158/0008-5472.CAN-12-266323436800
   PubMed Web of Science ®Google Scholar
• Cheung KJ, Ewald AJ. A collective route to metastasis: seeding by tumor cell clusters. Science. 2016;352(6282):167–169. doi:10.1126/science.aaf654627124449
   PubMed Web of Science ®Google Scholar
• Doglioni G, Parik S, Fendt SM. Interactions in the (pre)metastatic niche support metastasis formation. Front Oncol. 2019;9:219. doi:10.3389/fonc.2019.0021931069166
   PubMed Web of Science ®Google Scholar
• Krüger A. Premetastatic niche formation in the liver: emerging mechanisms and mouse models. J Mol Med (Berl). 2015;93(11):1193–1201. doi:10.1007/s00109-015-1342-726400831
   PubMed Web of Science ®Google Scholar
• Wortzel I, Dror S, Kenific CM, Lyden D. Exosome-mediated metastasis: communication from a distance. Dev Cell. 2019;49(3):347–360. doi:10.1016/j.devcel.2019.04.01131063754
   PubMed Web of Science ®Google Scholar
• Wang Y, Ding Y, Guo N, Wang S. MDSCs: key criminals of tumor pre-metastatic niche formation. Front Immunol. 2019;10:172. doi:10.3389/fimmu.2019.0017230792719
   PubMed Web of Science ®Google Scholar
• Seebauer CT, Brunner S, Glockzin G, et al. Peritoneal carcinomatosis of colorectal cancer is characterized by structural and functional reorganization of the tumor microenvironment inducing senescence and proliferation arrest in cancer cells. Oncoimmunology. 2016;5(12):e1242543. doi:10.1080/2162402X.2016.124254328439450
   PubMed Web of Science ®Google Scholar
• Chen XW, Yu TJ, Zhang J, et al. CYP4A in tumor-associated macrophages promotes pre-metastatic niche formation and metastasis. Oncogene. 2017;36(35):5045–5057. doi:10.1038/onc.2017.11828481877
   PubMed Web of Science ®Google Scholar
• Kong J, Tian H, Zhang F, et al. Extracellular vesicles of carcinoma-associated fibroblasts creates a pre-metastatic niche in the lung through activating fibroblasts. Mol Cancer. 2019;18(1):175. doi:10.1186/s12943-019-1101-431796058
   PubMed Web of Science ®Google Scholar
• Wu S, Zheng Q, Xing X, et al. Matrix stiffness-upregulated LOXL2 promotes fibronectin production, MMP9 and CXCL12 expression and BMDCs recruitment to assist pre-metastatic niche formation. J Exp Clin Cancer Res. 2018;37(1):99. doi:10.1186/s13046-018-0761-z29728125
   PubMedGoogle Scholar
• Roder JD, Busch R, Stein HJ, Fink U, Siewert JR. Ratio of invaded to removed lymph nodes as a predictor of survival in squamous cell carcinoma of the oesophagus. Br J Surg. 1994;81(3):410–413. doi:10.1002/bjs.18008103308173915
   PubMed Web of Science ®Google Scholar
• Shibata T, Takita K, Inomata M. Observation of the cytoarchitecture of the human esophageal mucosa with special attention to the lamina muscularis mucosae and the distribution of lymphatic vessels. Esophagus. 2019;16(1):44–51. doi:10.1007/s10388-018-0632-x30073428
   PubMed Web of Science ®Google Scholar
• Wang Y, Zhu L, Xia W, Wang F. Anatomy of lymphatic drainage of the esophagus and lymph node metastasis of thoracic esophageal cancer. Cancer Manag Res. 2018;10:6295–6303. doi:10.2147/CMAR.S18243630568491
   PubMed Web of Science ®Google Scholar
• Otto B, Koenig AM, Tolstonog GV, et al. Molecular changes in pre-metastatic lymph nodes of esophageal cancer patients. PLoS One. 2014;9(7):e102552. doi:10.1371/journal.pone.010255225048826
   PubMed Web of Science ®Google Scholar
• O’Sullivan GC, Corbett AR, Shanahan F, Collins JK. Regional immunosuppression in esophageal squamous cancer: evidence from functional studies with matched lymph nodes. J Immunol. 1996;157(10):4717–4720.8906853
   PubMed Web of Science ®Google Scholar
• Preynat-Seauve O, Contassot E, Schuler P, Piguet V, French LE, Huard B. Extralymphatic tumors prepare draining lymph nodes to invasion via a T-cell cross-tolerance process. Cancer Res. 2007;67(10):5009–5016. doi:10.1158/0008-5472.CAN-06-449417510433
   PubMed Web of Science ®Google Scholar
• Cochran AJ, Huang RR, Lee J, Itakura E, Leong SP, Essner R. Tumour-induced immune modulation of sentinel lymph nodes. Nat Rev Immunol. 2006;6(9):659–670. doi:10.1038/nri191916932751
   PubMed Web of Science ®Google Scholar
• Kim R, Emi M, Tanabe K, Arihiro K. Immunobiology of the sentinel lymph node and its potential role for antitumour immunity. Lancet Oncol. 2006;7(12):1006–1016. doi:10.1016/S1470-2045(06)70975-517138222
   PubMed Web of Science ®Google Scholar
• Campbell MJ, Baehner F, O’Meara T, et al. Characterizing the immune microenvironment in high-risk ductal carcinoma in situ of the breast. Breast Cancer Res Treat. 2017;161(1):17–28. doi:10.1007/s10549-016-4036-027785654
   PubMed Web of Science ®Google Scholar
• Gorringe KL, Fox SB. Ductal carcinoma in situ biology, biomarkers, and diagnosis. Front Oncol. 2017;7:248. doi:10.3389/fonc.2017.0024829109942
   PubMed Web of Science ®Google Scholar