Metformin Inducing the Change of Functional and Exhausted Phenotypic Tumor-Infiltrated Lymphocytes and the Correlation with JNK Signal Pathway in Triple-Negative Breast Cancer

References

• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. doi:10.3322/caac.21590
   PubMed Web of Science ®Google Scholar
• Zheng S, Bai JQ, Li J, et al. The pathologic characteristics of breast cancer in China and its shift during 1999–2008: a national-wide multicenter cross-sectional image over 10 years. Int J Cancer. 2012;131(11):2622–2631. doi:10.1002/ijc.27513
   PubMed Web of Science ®Google Scholar
• Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61–70. doi:10.1038/nature11412
   PubMed Web of Science ®Google Scholar
• Gatalica Z, Snyder C, Maney T, et al. Programmed cell death 1 (PD-1) and its ligand (PD-L1) in common cancers and their correlation with molecular cancer type. Cancer Epidemiol Biomarkers Prev. 2014;23(12):2965–2970. doi:10.1158/1055-9965.EPI-14-0654
   PubMed Web of Science ®Google Scholar
• Wang R, Shi F, Zhao L, Zhao Y, Wu G, Song QK. High expression of E-cadherin and Ki-67 associated with functional/dysfunctional phenotypes of tumor-infiltrating lymphocytes among Chinese patients with operable breast cancer. J Int Med Res 2018;46(12):5219–5227. doi:10.1177/0300060518799567
   Web of Science ®Google Scholar
• Verma R, Hanby AM, Horgan K, et al. Levels of different subtypes of tumour-infiltrating lymphocytes correlate with each other, with matched circulating lymphocytes, and with survival in breast cancer. Breast Cancer Res Treat. 2020;183(1):49–59. doi:10.1007/s10549-020-05757-5
   Web of Science ®Google Scholar
• Adams S, Gray RJ, Demaria S, et al. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two Phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014;32(27):2959–2966. doi:10.1200/JCO.2013.55.0491
   PubMed Web of Science ®Google Scholar
• Loi S, Michiels S, Salgado R, et al. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol. 2014;25(8):1544–1550. doi:10.1093/annonc/mdu112
   PubMed Web of Science ®Google Scholar
• Arneth B. Tumor microenvironment. Medicina. 2019;56(1). doi:10.3390/medicina56010015
   PubMed Web of Science ®Google Scholar
• Loi S, Dushyanthen S, Beavis PA, et al. Correction: RAS/MAPK activation is associated with reduced tumor-infiltrating lymphocytes in triple-negative breast cancer: therapeutic cooperation between MEK and PD-1/PD-L1 Immune Checkpoint Inhibitors. Clin Cancer Res. 2019;25(4):1437. doi:10.1158/1078-0432.CCR-18-4264
   Web of Science ®Google Scholar
• Blonska M, Lin X. CARMA1-mediated NF-kappaB and JNK activation in lymphocytes. Immunol Rev. 2009;228(1):199–211. doi:10.1111/j.1600-065X.2008.00749.x
   Web of Science ®Google Scholar
• Foretz M, Guigas B, Viollet B. Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus. Nat Rev Endocrinol. 2019;15(10):569–589. doi:10.1038/s41574-019-0242-2
   PubMed Web of Science ®Google Scholar
• Vancura A, Bu P, Bhagwat M, Zeng J, Vancurova I. Metformin as an anticancer agent. Trends Pharmacol Sci. 2018;39(10):867–878. doi:10.1016/j.tips.2018.07.006
   Web of Science ®Google Scholar
• Eikawa S, Nishida M, Mizukami S, Yamazaki C, Nakayama E, Udono H. Immune-mediated antitumor effect by type 2 diabetes drug, metformin. Proc Natl Acad Sci U S A. 2015;112(6):1809–1814. doi:10.1073/pnas.1417636112
   PubMed Web of Science ®Google Scholar
• Cha JH, Yang WH, Xia W, et al. Metformin promotes antitumor immunity via endoplasmic-reticulum-associated degradation of PD-L1. Mol Cell. 2018;71(4):606–620.e7. doi:10.1016/j.molcel.2018.07.030
   PubMed Web of Science ®Google Scholar
• Bahrambeigi S, Shafiei-Irannejad V. Immune-mediated anti-tumor effects of metformin; targeting metabolic reprogramming of T cells as a new possible mechanism for anti-cancer effects of metformin. Biochem Pharmacol. 2020;174:113787. doi:10.1016/j.bcp.2019.113787
   Web of Science ®Google Scholar
• Loubière C, Dirat B, Tanti JF, Bost F. Metformine et cancer : de nouvelles perspectives pour un ancien médicament [New perspectives for metformin in cancer therapy]. Ann Endocrinol. 2013;74(2):130–136. French. doi:10.1016/j.ando.2013.02.002
   Web of Science ®Google Scholar
• Daugan M, Dufaÿ Wojcicki A, d’Hayer B, Boudy V. Metformin: an anti-diabetic drug to fight cancer. Pharmacol Res. 2016;113:675–685. doi:10.1016/j.phrs.2016.10.006
   PubMed Web of Science ®Google Scholar
• Stanton SE, Disis ML. Clinical significance of tumor-infiltrating lymphocytes in breast cancer. J Immunother Cancer. 2016;4(1):59. doi:10.1186/s40425-016-0165-6
   PubMed Web of Science ®Google Scholar
• Pereira FV, Melo A, Low JS, et al. Metformin exerts antitumor activity via induction of multiple death pathways in tumor cells and activation of a protective immune response. Oncotarget. 2018;9(40):25808–25825. doi:10.18632/oncotarget.25380
   PubMedGoogle Scholar
• Xiao Y, Liu F, Li S, et al. Metformin promotes innate immunity through a conserved PMK-1/p38 MAPK pathway. Virulence. 2020;11(1):39–48. doi:10.1080/21505594.2019.1706305
   PubMed Web of Science ®Google Scholar
• Huang Y, Ma C, Zhang Q, et al. CD4+ and CD8+ T cells have opposing roles in breast cancer progression and outcome. Oncotarget. 2015;6(19):17462–17478. doi:10.18632/oncotarget.3958
   Google Scholar
• Sato E, Olson SH, Ahn J, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A. 2005;102(51):18538–18543. doi:10.1073/pnas.0509182102
   PubMed Web of Science ®Google Scholar
• Mahmoud SM, Paish EC, Powe DG, et al. An evaluation of the clinical significance of FOXP3+ infiltrating cells in human breast cancer. Breast Cancer Res Treat. 2011;127(1):99–108. doi:10.1007/s10549-010-0987-8
   Web of Science ®Google Scholar
• Lee S, Cho EY, Park YH, Ahn JS, Im YH. Prognostic impact of FOXP3 expression in triple-negative breast cancer. Acta Oncol. 2013;52(1):73–81. doi:10.3109/0284186X.2012.731520
   PubMed Web of Science ®Google Scholar
• Kunisada Y, Eikawa S, Tomonobu N, et al. Attenuation of CD4+CD25+ regulatory T cells in the tumor microenvironment by metformin, a type 2 diabetes drug. EBioMedicine. 2017;25:154–164. doi:10.1016/j.ebiom.2017.10.009
   PubMed Web of Science ®Google Scholar
• Heasley LE, Han SY. JNK regulation of oncogenesis. Mol Cells. 2006;21(2):167–173.
   PubMed Web of Science ®Google Scholar
• Weiss L, Whitmarsh AJ, Yang DD, Rincón M, Davis RJ, Flavell RA. Regulation of c-Jun NH(2)-terminal kinase (Jnk) gene expression during T cell activation. J Exp Med. 2000;191(1):139–146. doi:10.1084/jem.191.1.139
   Web of Science ®Google Scholar
• Steven A, Friedrich M, Jank P, et al. What turns CREB on? And off? And why does it matter. Cell Mol Life Sci. 2020;77(20):4049–4067. doi:10.1007/s00018-020-03525-8
   Web of Science ®Google Scholar
• Lucien F, Brochu-Gaudreau K, Arsenault D, Harper K, Dubois CM, Welm AL. Hypoxia-induced invadopodia formation involves activation of NHE-1 by the p90 ribosomal S6 kinase (p90RSK). PLoS One. 2011;6(12):e28851. doi:10.1371/journal.pone.0028851
   PubMed Web of Science ®Google Scholar
• Romeo Y, Zhang X, Roux PP. Regulation and function of the RSK family of protein kinases. Biochem J. 2012;441(2):553–569. doi:10.1042/BJ20110289
   PubMed Web of Science ®Google Scholar
• Muenst S, Schaerli AR, Gao F, et al. Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat. 2014;146(1):15–24. doi:10.1007/s10549-014-2988-5
   PubMed Web of Science ®Google Scholar
• Muenst S, Soysal SD, Gao F, Obermann EC, Oertli D, Gillanders WE. The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat. 2013;139(3):667–676. doi:10.1007/s10549-013-2581-3
   PubMed Web of Science ®Google Scholar
• Loi S, Dushyanthen S, Beavis PA, et al. RAS/MAPK activation is associated with reduced tumor-infiltrating lymphocytes in triple-negative breast cancer: therapeutic cooperation between MEK and PD-1/PD-L1 immune checkpoint inhibitors. Clin Cancer Res. 2016;22(6):1499–1509. doi:10.1158/1078-0432.CCR-15-1125
   PubMed Web of Science ®Google Scholar
• Hsieh S-C, Tsai J-P, Yang S-F, Tang M-J, Hsieh Y-H. Metformin inhibits the invasion of human hepatocellular carcinoma cells and enhances the chemosensitivity to sorafenib through a downregulation of the ERK/JNK-mediated NF-κB-dependent pathway that reduces uPA and MMP-9 expression. Amino Acids. 2014;46(12):2809–2822. doi:10.1007/s00726-014-1838-4
   PubMed Web of Science ®Google Scholar
• Chamoto K, Al-Habsi M, Honjo T. Role of PD-1 in immunity and diseases. Curr Top Microbiol Immunol. 2017;410:75–97. doi:10.1007/82_2017_67
   PubMed Web of Science ®Google Scholar
• Li F, Ren Y, Wang Z. Programmed death 1 Ligand 1 expression in breast cancer and its association with patients’ clinical parameters. J Cancer Res Ther. 2018;14(1):150–154. doi:10.4103/jcrt.JCRT_602_17
   PubMed Web of Science ®Google Scholar
• Brusa D, Serra S, Coscia M, et al. The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia. Haematologica. 2013;98(6):953–963. doi:10.3324/haematol.2012.077537
   PubMed Web of Science ®Google Scholar
• van Vught LA, Wiewel MA, Hoogendijk AJ, et al. The host response in patients with sepsis developing intensive care unit-acquired secondary infections. Am J Respir Crit Care Med. 2017;196(4):458–470. doi:10.1164/rccm.201606-1225OC
   PubMed Web of Science ®Google Scholar
• Hotchkiss RS, Colston E, Yende S, et al. Immune checkpoint inhibition in sepsis: a Phase 1b randomized study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of nivolumab. Intensive Care Med. 2019;45(10):1360–1371. doi:10.1007/s00134-019-05704-z
   PubMed Web of Science ®Google Scholar
• Nakae S, Suto H, Iikura M, et al. Mast cells enhance T cell activation: importance of mast cell costimulatory molecules and secreted TNF. J Immunol. 2006;176(4):2238–2248. doi:10.4049/jimmunol.176.4.2238
   Web of Science ®Google Scholar
• Takemura Y, Osuga Y, Yoshino O, et al. Metformin suppresses interleukin (IL)-1β-Induced IL-8 production, aromatase activation, and proliferation of endometriotic stromal cells. J Clin Endocrinol Metab. 2007;92(8):3213–3218. doi:10.1210/jc.2006-2486
   PubMed Web of Science ®Google Scholar
• Yu H, Pardoll D, Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nat Rev Cancer. 2009;9(11):798–809. doi:10.1038/nrc2734
   PubMed Web of Science ®Google Scholar
• Choi YK, Park KG. Metabolic roles of AMPK and metformin in cancer cells. Mol Cells. 2013;36(4):279–287. doi:10.1007/s10059-013-0169-8
   Web of Science ®Google Scholar
• Salminen A, Hyttinen JM, Kaarniranta K. AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan. J Mol Med. 2011;89(7):667–676. doi:10.1007/s00109-011-0748-0
   PubMed Web of Science ®Google Scholar
• O’Donnell JS, Teng M, Smyth MJ. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol. 2019;16(3):151–167. doi:10.1038/s41571-018-0142-8
   PubMed Web of Science ®Google Scholar
• Kim TH, Suh DH, Kim MK, Song YS. Metformin against cancer stem cells through the modulation of energy metabolism: special considerations on ovarian cancer. Biomed Res Int. 2014;2014:132702. doi:10.1155/2014/132702
   Web of Science ®Google Scholar
• Zhou H, Liu J, Zhang Y, Zhang L. Inflammatory bowel disease associated with the combination treatment of nivolumab and metformin: data from the FDA adverse event reporting system. Cancer Chemother Pharmacol. 2019;83(3):599–601. doi:10.1007/s00280-018-03763-5
   Web of Science ®Google Scholar