Lymphatic vessel density is associated with CD8⁺ T cell infiltration and immunosuppressive factors in human melanoma

References

• Farkona S, Diamandis EP, Blasutig IM. Cancer immunotherapy: the beginning of the end of cancer? BMC Med. 2016;14:73. doi:10.1186/s12916-016-0623-5. PMID:27151159.
   PubMed Web of Science ®Google Scholar
• Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015;161:205–14. doi:10.1016/j.cell.2015.03.030. PMID:25860605.
   PubMed Web of Science ®Google Scholar
• Maus MV, Fraietta JA, Levine BL, Kalos M, Zhao Y, June CH. Adoptive immunotherapy for cancer or viruses. Annu Rev Immunol. 2014;32:189–225. doi:10.1146/annurev-immunol-032713-120136. PMID:24423116.
   PubMed Web of Science ®Google Scholar
• Peggs KS, Quezada SA, Allison JP. Cancer immunotherapy: Co-stimulatory agonists and co-inhibitory antagonists. Clin Exp Immunol. 2009;157:9–19. doi:10.1111/j.1365-2249.2009.03912.x. PMID:19659765.
   PubMed Web of Science ®Google Scholar
• Hamid O, Robert C, Daud A, Hodi FS, Hwu W-J, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS, et al. Safety and Tumor Responses with Lambrolizumab (Anti–PD-1) in Melanoma. N Engl J Med. 2013;369:134–44. doi:10.1056/NEJMoa1305133. PMID:23724846.
   PubMed Web of Science ®Google Scholar
• Inoue H, Park J-H, Kiyotani K, Zewde M, Miyashita A, Jinnin M, Kiniwa Y, Okuyama R, Tanaka R, Fujisawa Y, et al. Intratumoral expression levels of PD-L1, GZMA, and HLA-A along with oligoclonal T cell expansion associate with response to nivolumab in metastatic melanoma. oncoimmunology. 2016;5:1–7. doi:10.1080/2162402X.2016.1204507.
   Web of Science ®Google Scholar
• Ulloa-Montoya F, Louahed J, Dizier B, Gruselle O, Spiessens B, Lehmann FF, Suciu S, Kruit WHJ, Eggermont AMM, Vansteenkiste J, et al. Predictive Gene Signature in MAGE-A3 Antigen-Specific Cancer Immunotherapy. J Clin Oncol. 2013;31:2388–95. doi:10.1200/JCO.2012.44.3762. PMID:23715562.
   PubMed Web of Science ®Google Scholar
• Spranger S, Spaapen RM, Zha Y, Williams J, Meng Y, Ha TT, Gajewski TF. Up-Regulation of PD-L1, IDO, and Tregs in the Melanoma Tumor Microenvironment Is Driven by CD8+ T Cells. Sci Transl Med. 2013;5:200ra116–6. doi:10.1126/scitranslmed.3006504. PMID:23986400.
   PubMed Web of Science ®Google Scholar
• Liu C, Peng W, Xu C, Lou Y, Zhang M, Wargo JA, Chen J, Li HS, Watowich S, Yang Y, et al. BRAF Inhibition Increases Tumor Infiltration by T cells and Enhances the Anti-tumor Activity of Adoptive Immunotherapy in Mice. Clin Cancer Res. 2013 Jan 15;19(2):393–403. doi:10.1158/1078-0432.CCR-12-1626.
   PubMed Web of Science ®Google Scholar
• Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, Chen S, Klein AP, Pardoll DM, Topalian SL, et al. Colocalization of Inflammatory Response with B7-H1 Expression in Human Melanocytic Lesions Supports an Adaptive Resistance Mechanism of Immune Escape. Sci Transl Med. 2012;4:127ra37–7. doi:10.1126/scitranslmed.3003689. PMID:22461641.
   PubMed Web of Science ®Google Scholar
• Ribas A. Adaptive Immune Resistance: How Cancer Protects from Immune Attack. Cancer Discov. 2015;5:915–9. doi:10.1158/2159-8290.CD-15-0563. PMID:26272491.
   PubMed Web of Science ®Google Scholar
• Spranger S, Gajewski TF. Impact of oncogenic pathways on evasion of antitumour immune responses. Nat Rev Cancer. 2018;1–9. PMID:29217839.
   PubMed Web of Science ®Google Scholar
• Netzer R, Fleishman SJ. Inspired by nature. Science 2016;352:657–8. doi:10.1126/science.aaf7599. PMID:27151851.
   PubMed Web of Science ®Google Scholar
• Skobe M, Hawighorst T, Jackson DG, Prevo R, Janes L, Velasco P, Riccardi L, Alitalo K, Claffey K, Detmar M. Induction of tumor lymphangiogenesis by VEGF-C promotes breast cancer metastasis. Nat Med. 2001;7:192–8. doi:10.1038/84643. PMID:11175850.
   PubMed Web of Science ®Google Scholar
• Stacker SA, Caesar C, Baldwin ME, Thornton GE, Williams RA, Prevo R, Jackson DG, Nishikawa S, Kubo H, Achen MG. VEGF-D promotes the metastatic spread of tumor cells via the lymphatics. Nat Med. 2001;7:186–91. doi:10.1038/84635. PMID:11175849.
   PubMed Web of Science ®Google Scholar
• Dadras SS, Paul T, Bertoncini J, Brown LF, Muzikansky A, Jackson DG, Ellwanger U, Garbe C, Mihm MC, Detmar M. Tumor lymphangiogenesis: A novel prognostic indicator for cutaneous melanoma metastasis and survival. Am J Pathol. 2003;162:1951–60. doi:10.1016/S0002-9440(10)64328-3. PMID:12759251.
   PubMed Web of Science ®Google Scholar
• Schietroma C, Cianfarani F, Lacal PM, Odorisio T, Orecchia A, Kanitakis J, D'Atri S, Failla CM, Zambruno G. Vascular endothelial growth factor-C expression correlates with lymph node localization of human melanoma metastases. Cancer. 2003 Aug 15;98(4):789–97. doi:10.1002/cncr.11583.
   PubMed Web of Science ®Google Scholar
• Mandriota SJ. Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J. 2001;20:672–82. doi:10.1093/emboj/20.4.672. PMID:11179212.
   PubMed Web of Science ®Google Scholar
• Rinderknecht M, Detmar M. Tumor lymphangiogenesis and melanoma metastasis. J Cell Physiol. 2008;216:347–54. doi:10.1002/jcp.21494. PMID:18481261.
   PubMed Web of Science ®Google Scholar
• Christiansen A, Detmar M. Lymphangiogenesis and Cancer. Genes Cancer. 2011 Dec;2(12):1146–58. doi:10.1177/1947601911423028.
   PubMedGoogle Scholar
• Issa A, Le TX, Shoushtari AN, Shields JD, Swartz MA. Vascular endothelial growth factor-C and C-C chemokine receptor 7 in tumor cell-lymphatic cross-talk promote invasive phenotype. Cancer Res. 2009;69:349–57. doi:10.1158/0008-5472.CAN-08-1875. PMID:19118020.
   PubMed Web of Science ®Google Scholar
• Shields JD, Fleury ME, Yong C, Tomei AA, Randolph GJ, Swartz MA. Autologous chemotaxis as a mechanism of tumor cell homing to lymphatics via interstitial flow and autocrine CCR7 signaling. Cancer Cell. 2007;11:526–38. doi:10.1016/j.ccr.2007.04.020. PMID:17560334.
   PubMed Web of Science ®Google Scholar
• Shields JD, Emmett MS, Dunn DBA, Joory KD, Sage LM, Rigby H, Mortimer PS, Orlando A, Levick JR, Bates DO. Chemokine-mediated migration of melanoma cells towards lymphatics–a mechanism contributing to metastasis. Oncogene. 2007;26:2997–3005. doi:10.1038/sj.onc.1210114. PMID:17130836.
   PubMed Web of Science ®Google Scholar
• Shields JD, Kourtis IC, Tomei AA, Roberts JM, Swartz MA. Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21. Science. 2010;328:749–52. doi:10.1126/science.1185837. PMID:20339029.
   PubMed Web of Science ®Google Scholar
• Lund AW, Duraes FV, Hirosue S, Raghavan VR, Nembrini C, Thomas SN, Issa A, Hugues S, Swartz MA. VEGF-C promotes immune tolerance in B16 melanomas and cross-presentation of tumor antigen by lymph node lymphatics. Cell Rep. 2012;1:191–9. doi:10.1016/j.celrep.2012.01.005. PMID:22832193.
   PubMed Web of Science ®Google Scholar
• Hirosue S, Vokali E, Raghavan VR, Rincon-Restrepo M, Lund AW, Corthésy-Henrioud P, Capotosti F, Halin Winter C, Hugues S, Swartz MA. Steady-state antigen scavenging, cross-presentation, and CD8+ T cell priming: A new role for lymphatic endothelial cells. J Immunol. 2014;192:5002–11. doi:10.4049/jimmunol.1302492. PMID:24795456.
   PubMed Web of Science ®Google Scholar
• Podgrabinska S, Kamalu O, Mayer L, Shimaoka M, Snoeck H, Randolph GJ, Skobe M. Inflamed lymphatic endothelium suppresses dendritic cell maturation and function via Mac-1/ICAM-1-dependent mechanism. J Immunol. 2009;183:1767–79. doi:10.4049/jimmunol.0802167. PMID:19587009.
   PubMed Web of Science ®Google Scholar
• Swartz MA, Lund AW. Lymphatic and interstitial flow in the tumour microenvironment: linking mechanobiology with immunity. Nat Rev Cancer. 2012 Feb 24;12(3):210–9. doi:10.1038/nrc3186.
   PubMed Web of Science ®Google Scholar
• Lund AW, Wagner M, Fankhauser M, Steinskog ES, Broggi MA, Spranger S, Gajewski TF, Alitalo K, Eikesdal HP, Wiig H, et al. Lymphatic vessels regulate immune microenvironments in human and murine melanoma. J Clin Invest. 2016;126:3389–402. doi:10.1172/JCI79434. PMID:27525437.
   PubMed Web of Science ®Google Scholar
• Pastushenko I, Conejero C, Carapeto FJ. Lymphangiogenesis: Implications for Diagnosis, Treatment, and Prognosis in Patients With Melanoma. Actas Dermo-Sifiliográficas ( English Edition). 2015;106:7–16. doi:10.1016/j.adengl.2014.11.001.
   PubMed Web of Science ®Google Scholar
• Dadras SS, Lange-Asschenfeldt B, Velasco P, Nguyen L, Vora A, Muzikansky A, Jahnke K, Hauschild A, Hirakawa S, Mihm MC, et al. Tumor lymphangiogenesis predicts melanoma metastasis to sentinel lymph nodes. Mod Pathol. 2005;18:1232–42. doi:10.1038/modpathol.3800410. PMID:15803182.
   PubMed Web of Science ®Google Scholar
• Giorgadze TA, Zhang PJ, Pasha T, Coogan PS, Acs G, Elder DE, Xu X. Lymphatic vessel density is significantly increased in melanoma. J Cutan Pathol. 2004;31:672–7. doi:10.1111/j.0303-6987.2004.00249.x. PMID:15491327.
   PubMed Web of Science ®Google Scholar
• Shields JD, Borsetti M, Rigby H, Harper SJ, Mortimer PS, Levick JR, Orlando A, Bates DO. Lymphatic density and metastatic spread in human malignant melanoma. Br J Cancer. 2004;90:693–700. doi:10.1038/sj.bjc.6601571. PMID:14760386.
   PubMed Web of Science ®Google Scholar
• Massi D, De Nisi MC, Franchi A, Mourmouras V, Baroni G, Panelos J, Santucci M, Miracco C. Inducible nitric oxide synthase expression in melanoma: implications in lymphangiogenesis. Mod Pathol. 2009;22:21–30. doi:10.1038/modpathol.2008.128. PMID:18660796.
   PubMed Web of Science ®Google Scholar
• Hirakawa S, Brown LF, Kodama S, Paavonen K, Alitalo K, Detmar M. VEGF-C-induced lymphangiogenesis in sentinel lymph nodes promotes tumor metastasis to distant sites. Blood. 2007;109:1010–7. doi:10.1182/blood-2006-05-021758. PMID:17032920.
   PubMed Web of Science ®Google Scholar
• Harrell MI, Iritani BM, Ruddell A. Tumor-induced sentinel lymph node lymphangiogenesis and increased lymph flow precede melanoma metastasis. Am J Pathol. 2007;170:774–86. doi:10.2353/ajpath.2007.060761. PMID:17255343.
   PubMed Web of Science ®Google Scholar
• Cochran AJ, Huang R-R, Lee J, Itakura E, Leong SPL, Essner R. Tumour-induced immune modulation of sentinel lymph nodes. Nat Rev Immunol. 2006;6:659–70. doi:10.1038/nri1919. PMID:16932751.
   PubMed Web of Science ®Google Scholar
• Pasquali S, van der Ploeg APT, Mocellin S, Stretch JR, Thompson JF, Scolyer RA. Lymphatic biomarkers in primary melanomas as predictors of regional lymph node metastasis and patient outcomes. Pigment Cell Melanoma Res. 2013;26:326–37. doi:10.1111/pcmr.12064. PMID:23298266.
   PubMed Web of Science ®Google Scholar
• Lund AW, Medler TR, Leachman SA, Coussens LM. Lymphatic Vessels, Inflammation, and Immunity in Skin Cancer. Cancer Discov. 2016;6:22–35. doi:10.1158/2159-8290.CD-15-0023. PMID:26552413.
   PubMed Web of Science ®Google Scholar
• Stacker SA, Williams SP, Karnezis T, Shayan R, Fox SB, Achen MG. Lymphangiogenesis and lymphatic vessel remodelling in cancer. Nat Rev Cancer. 2014;14:159–72. doi:10.1038/nrc3677. PMID:24561443.
   PubMed Web of Science ®Google Scholar
• Boone B, Blokx W, De Bacquer D, Lambert J, Ruiter D, Brochez L. The role of VEGF-C staining in predicting regional metastasis in melanoma. Virchows Arch. 2008;453:257–65. doi:10.1007/s00428-008-0641-6. PMID:18679715.
   PubMed Web of Science ®Google Scholar
• Pastushenko I, Vermeulen PB, Carapeto FJ, Van den Eynden G, Rutten A, Ara M, Dirix LY, Van Laere S. Blood microvessel density, lymphatic microvessel density and lymphatic invasion in predicting melanoma metastases: systematic review and meta-analysis. Br J Dermatol. 2014;170:66–77. doi:10.1111/bjd.12688. PMID:24134623.
   PubMed Web of Science ®Google Scholar
• Massi D. Tumour lymphangiogenesis is a possible predictor of sentinel lymph node status in cutaneous melanoma: a case-control study. Journal of Clinical Pathology 2006;59:166–73. doi:10.1136/jcp.2005.028431. PMID:16443733.
   PubMed Web of Science ®Google Scholar
• Tewalt EF, Cohen JN, Rouhani SJ, Guidi CJ, Qiao H, Fahl SP, Conaway MR, Bender TP, Tung KS, Vella AT, et al. Lymphatic endothelial cells induce tolerance via PD-L1 and lack of costimulation leading to high-level PD-1 expression on CD8 T cells. Blood. 2012 Dec 6;120(24):4772–82. doi:10.1182/blood-2012-04-427013.
   PubMed Web of Science ®Google Scholar
• Van der Auwera I, Cao Y, Tille JC, Pepper MS, Jackson DG, Fox SB, Harris AL, Dirix LY, Vermeulen PB. First international consensus on the methodology of lymphangiogenesis quantification in solid human tumours. Br J Cancer. 2006 Dec 18;95(12):1611–25. doi:10.1038/sj.bjc.6603445.
   PubMed Web of Science ®Google Scholar
• Straume O, Jackson DG, Akslen LA. Independent prognostic impact of lymphatic vessel density and presence of low-grade lymphangiogenesis in cutaneous melanoma. Clin Cancer Res. 2003;9:250–6. PMID:12538477.
   PubMed Web of Science ®Google Scholar
• Valencak J, Heere-Ress E, Kopp T, Schoppmann SF, Kittler H, Pehamberger H. Selective immunohistochemical staining shows significant prognostic influence of lymphatic and blood vessels in patients with malignant melanoma. Eur J Cancer. 2004;40:358–64. doi:10.1016/j.ejca.2003.09.009. PMID:14746853.
   PubMed Web of Science ®Google Scholar
• Gannon PO, Poisson AO, Delvoye N, Lapointe R, Mes-Masson A-M, Saad F. Characterization of the intra-prostatic immune cell infiltration in androgen-deprived prostate cancer patients. J Immunol Methods. 2009;348:9–17. doi:10.1016/j.jim.2009.06.004. PMID:19552894.
   PubMed Web of Science ®Google Scholar
• Toader MP, Ţăranu T, Toader Ş, Chirana A, Ţăranu T. Correlation between lymphatic vessel density and microvessel density in cutaneous malignant melanoma. Rom J Morphol Embryol. 2014;55:141–5. PMID:24715179.
   PubMed Web of Science ®Google Scholar
• Shayan R, Karnezis T, Murali R, Wilmott JS, Ashton MW, Taylor GI, Thompson JF, Hersey P, Achen MG, Scolyer RA, et al. Lymphatic vessel density in primary melanomas predicts sentinel lymph node status and risk of metastasis. Histopathology. 2012 Oct;61(4):702–10. doi:10.1111/j.1365-2559.2012.04310.x.
   PubMed Web of Science ®Google Scholar
• Sahni D, Robson A, Orchard G, Szydlo R, Evans AV, Russell-Jones R. The use of LYVE-1 antibody for detecting lymphatic involvement in patients with malignant melanoma of known sentinel node status. Journal of Clinical Pathology. 2005;58:715–21. doi:10.1136/jcp.2004.020123. PMID:15976338.
   PubMed Web of Science ®Google Scholar
• Tammela T, Alitalo K. Lymphangiogenesis: Molecular mechanisms and future promise. Cell. 2010;140:460–76. doi:10.1016/j.cell.2010.01.045. PMID:20178740.
   PubMed Web of Science ®Google Scholar
• Dieu Nosjean MC, Giraldo NA, Kaplon H, Germain C, Fridman W-H, Sautès-Fridman C. Tertiary lymphoid structures, drivers of the anti‐tumor responses in human cancers. Immunol Rev. 2016;271:260–75. doi:10.1111/imr.12405. PMID:27088920.
   PubMed Web of Science ®Google Scholar
• Avram G, Sánchez-Sendra B, Martín JM, Terrádez L, Ramos D, Monteagudo C. The density and type of MECA-79-positive high endothelial venules correlate with lymphocytic infiltration and tumour regression in primary cutaneous melanoma. Histopathology. 2013;63:852–61. doi:10.1111/his.12235. PMID:24102908.
   PubMed Web of Science ®Google Scholar
• Martinet L, Le Guellec S, Filleron T, Lamant L, Meyer N, Rochaix P, Garrido I, Girard J-P. High endothelial venules (HEVs) in human melanoma lesions: Major gateways for tumor-infiltrating lymphocytes. oncoimmunology. 2012;1:829–39. doi:10.4161/onci.20492. PMID:23162750.
   PubMed Web of Science ®Google Scholar
• van Baren N, Baurain J-F, Coulie PG. Lymphoid neogenesis in melanoma: What does it tell us?. Oncoimmunology. 2013 Jan 1;2(1):e22505. doi:10.4161/onci.22505.
   PubMed Web of Science ®Google Scholar
• Ladányi A, Sebestyén T, Mohos A, Liszkay G, Somlai B, Tóth E, Timar J. Ectopic lymphoid structures in primary cutaneous melanoma. Pathol Oncol Res. 2014;20:981–5. doi:10.1007/s12253-014-9784-8. PMID:24781762.
   PubMed Web of Science ®Google Scholar
• Card CM, Yu SS, Swartz MA. Emerging roles of lymphatic endothelium in regulating adaptive immunity. J Clin Invest. 2014;124:943–52. doi:10.1172/JCI73316. PMID:24590280.
   PubMed Web of Science ®Google Scholar
• Lukacs-Kornek V, Malhotra D, Fletcher AL, Acton SE, Elpek KG, Tayalia P, Collier A-R, Turley SJ. Regulated release of nitric oxide by nonhematopoietic stroma controls expansion of the activated T cell pool in lymph nodes. Nat Immunol. 2011;12:1096–104. doi:10.1038/ni.2112. PMID:21926986.
   PubMed Web of Science ®Google Scholar
• Nörder M, Gutierrez MG, Zicari S, Cervi E, Caruso A, Guzmán CA. Lymph node-derived lymphatic endothelial cells express functional costimulatory molecules and impair dendritic cell-induced allogenic T-cell proliferation. FASEB J. 2012;26:2835–46. doi:10.1096/fj.12-205278. PMID:22459150.
   PubMed Web of Science ®Google Scholar
• Lee E, Pandey NB, Popel AS. Crosstalk between cancer cells and blood endothelial and lymphatic endothelial cells in tumour and organ microenvironment. Expert Rev Mol Med. 2015;17:e3. doi:10.1017/erm.2015.2. PMID:25634527.
   PubMed Web of Science ®Google Scholar
• Ferguson AR, Nichols LA, Zarling AL, Thompson ED, Brinkman CC, Hargadon KM, Bullock TN, Engelhard VH. Strategies and challenges in eliciting immunity to melanoma. Immunol Rev. 2008;222:28–42. doi:10.1111/j.1600-065X.2008.00620.x. PMID:18363993.
   PubMed Web of Science ®Google Scholar
• Fridman W-H, Remark R, Goc J, Giraldo NA, Becht E, Hammond SA, Damotte D, Dieu-Nosjean M-C, Sautès-Fridman C. The immune microenvironment: a major player in human cancers. Int Arch Allergy Immunol. 2014;164:13–26. doi:10.1159/000362332. PMID:24852691.
   PubMed Web of Science ®Google Scholar
• Fridman W-H, Pagès F, Sautès-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12:298–306. doi:10.1038/nrc3245. PMID:22419253.
   PubMed Web of Science ®Google Scholar
• Zuckerman NS, Yu H, Simons DL, Bhattacharya N, Carcamo-Cavazos V, Yan N, Dirbas FM, Johnson DL, Schwartz EJ, Lee PP. Altered local and systemic immune profiles underlie lymph node metastasis in breast cancer patients. Int J Cancer. 2013;132:2537–47. doi:10.1002/ijc.27933. PMID:23136075.
   PubMed Web of Science ®Google Scholar
• Spranger S, Gajewski TF. Tumor-intrinsic oncogene pathways mediating immune avoidance. oncoimmunology. 2016;5:1–7. doi:10.1080/2162402X.2015.1086862.
   Web of Science ®Google Scholar
• Fankhauser M, Broggi MA, Potin L, Bordry N, Jeanbart L, Lund AW, Da Costa E, Hauert S, Rincon-Restrepo M, Tremblay C, et al. Tumor lymphangiogenesis promotes T cell infiltration and potentiates immunotherapy in melanoma. Sci Transl Med. 2017 Sep 13;9:eaal4712. doi:10.1126/scitranslmed.aal4712.
   PubMed Web of Science ®Google Scholar
• Johansson-Percival A, He B, Li Z-J, Kjellén A, Russell K, Li J, Larma I, Ganss R. De novo induction of intratumoral lymphoid structures and vessel normalization enhances immunotherapy in resistant tumors. Nat Immunol. 2017;18:1207–17. doi:10.1038/ni.3836. PMID:28892469.
   PubMed Web of Science ®Google Scholar
• Speiser DE, Liénard D, Rufer N, Rubio-Godoy V, Rimoldi D, Lejeune F, Krieg AM, Cerottini J-C, Romero P. Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909. J Clin Invest. 2005;115:739–46. doi:10.1172/JCI23373. PMID:15696196.
   PubMed Web of Science ®Google Scholar
• Baumgaertner P, Jandus C, Rivals J-P, Derré L, Lövgren T, Baitsch L, Guillaume P, Luescher IF, Berthod G, Matter M, et al. Vaccination-induced functional competence of circulating human tumor-specific CD8 T-cells. Int J Cancer. 2012;130:2607–17. doi:10.1002/ijc.26297. PMID:21796616.
   PubMed Web of Science ®Google Scholar
• Kan S, Konishi E, Arita T, Ikemoto C, Takenaka H, Yanagisawa A, Katoh N, Asai J. Podoplanin expression in cancer-associated fibroblasts predicts aggressive behavior in melanoma. J Cutan Pathol. 2014;41:561–7. doi:10.1111/cup.12322. PMID:24588302.
   PubMed Web of Science ®Google Scholar