The PD-L1/PD-1 pathway promotes dysfunction, but not “exhaustion”, in tumor-responding T cells from pleural effusions in lung cancer patients

Cancer Immunology, Immunotherapy

Volumn 66, Issue 6, 2017, Pages 765-776

  Prado Garcia, Heriberto ^a   Romero Garcia, Susana ^a   Puerto Aquino, Alejandra ^a   Rumbo Nava, Uriel ^a  

^a INSTITUTO NACIONAL DE ENFERMEDADES RESPIRATORIAS   (Mexico)

Author keywords

CD8+ T cell; Lung cancer; Melanoma associated antigen 3 (MAGE 3A); PD L1 PD 1 pathway; T cell immunoglobulin domain and mucin domain protein 3 (TIM 3); Wilms tumor protein (WT 1)

Indexed keywords

BLOCKING ANTIBODY; CD137 ANTIGEN; CYTOMEGALOVIRUS ANTIGEN PP65; GAMMA INTERFERON; GRANZYME B; MELANOMA ANTIGEN 3; MELANOMA ANTIGEN 3A; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 RECEPTOR; UNCLASSIFIED DRUG; WT1 PROTEIN; CD274 PROTEIN, HUMAN;

ARTICLE; CANCER PATIENT; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; EFFECTOR CELL; FLOW CYTOMETRY; HUMAN; HUMAN CELL; HYPOXIA; IN VITRO STUDY; LUNG CANCER; LUNG CANCER CELL LINE; LUNG FIBROBLAST; LYMPHOCYTE DIFFERENTIATION; MALIGNANT PLEURA EFFUSION; MEMORY T LYMPHOCYTE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; T LYMPHOCYTE ACTIVATION; TUMOR CELL; UPREGULATION; ADENOCARCINOMA; ADULT; AGED; CELL CULTURE; FEMALE; GENE EXPRESSION REGULATION; IMMUNOLOGY; LUNG TUMOR; MALE; MESOTHELIOMA; METABOLISM; MIDDLE AGED; PATHOLOGY; PLEURA EFFUSION; SIGNAL TRANSDUCTION; SQUAMOUS CELL CARCINOMA; T LYMPHOCYTE SUBPOPULATION; VERY ELDERLY;

ADENOCARCINOMA; ADULT; AGED; AGED, 80 AND OVER; ANTIGENS, CD274; CARCINOMA, SQUAMOUS CELL; CELLS, CULTURED; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; LUNG NEOPLASMS; MALE; MESOTHELIOMA; MIDDLE AGED; PLEURAL EFFUSION; PROGRAMMED CELL DEATH 1 RECEPTOR; SIGNAL TRANSDUCTION; T-LYMPHOCYTE SUBSETS;

EID: 85015044182     PISSN: 03407004     EISSN: 14320851     Source Type: Journal    
DOI: 10.1007/s00262-017-1979-x     Document Type: Article

References (33)

1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108. doi:10.3322/caac.21262
2. Atanackovic D, Block A, de Weerth A, Faltz C, Hossfeld DK, Hegewisch-Becker S (2004) Characterization of effusion-infiltrating T cells: benign versus malignant effusions. Clin Cancer Res 10:2600–2608. doi:10.1158/1078-0432.CCR-03-0239
3. Prado-Garcia H, Aguilar-Cazares D, Flores-Vergara H, Mandoki JJ, Lopez-Gonzalez JS (2005) Effector, memory and naive CD8+ T cells in peripheral blood and pleural effusion from lung adenocarcinoma patients. Lung Cancer 47:361–371. doi:10.1016/j.lungcan.2004.07.046
4. Prado-Garcia H, Romero-Garcia S, Aguilar-Cazares D, Meneses-Flores M, Lopez-Gonzalez JS (2012) Tumor-induced CD8+ T-cell dysfunction in lung cancer patients. Clin Dev Immunol 2012:741741. doi:10.1155/2012/741741
5. Blank C, Mackensen A (2007) Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion. Cancer Immunol Immunother 56:739–745. doi:10.1007/s00262-006-0272-1
6. Okazaki T, Honjo T (2007) PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol 19:813–824. doi:10.1093/intimm/dxm057
7. Wherry EJ, Kurachi M (2015) Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol 15:486–499. doi:10.1038/nri3862
8. Prado-Garcia H, Romero-Garcia S, Lopez-Gonzalez JS (2015) The role of exhaustion in tumor-induced T cell dysfunction in cancer. In: Rezaei N (ed) Cancer immunology: a translational medicine context. Springer, Berlin, pp 61–75
9. Lopez-Gonzalez JS, Prado-Garcia H, Aguilar-Cazares D, Molina-Guarneros JA, Morales-Fuentes J, Mandoki JJ (2004) Apoptosis and cell cycle disturbances induced by coumarin and 7-hydroxycoumarin on human lung carcinoma cell lines. Lung Cancer 43:275–283. doi:10.1016/j.lungcan.2003.09.005
10. Prado-Garcia H, Aguilar-Cazares D, Meneses-Flores M, Morales-Fuentes J, Lopez-Gonzalez JS (2008) Lung carcinomas do not induce T-cell apoptosis via the Fas/Fas ligand pathway but down-regulate CD3 epsilon expression. Cancer Immunol Immunother 57:325–336. doi:10.1007/s00262-007-0372-6
11. He XH, Xu LH, Liu Y (2005) Identification of a novel splice variant of human PD-L1 mRNA encoding an isoform-lacking Igv-like domain. Acta Pharmacol Sin 26:462–468. doi:10.1111/j.1745-7254.2005.00086.x
12. Chan LY, Yim EK, Choo AB (2013) Normalized median fluorescence: an alternative flow cytometry analysis method for tracking human embryonic stem cell states during differentiation. Tissue Eng Part C Methods 19:156–165. doi:10.1089/ten.TEC.2012.0150
13. Sun J, Xu K, Wu C et al (2007) PD-L1 expression analysis in gastric carcinoma tissue and blocking of tumor-associated PD-L1 signaling by two functional monoclonal antibodies. Tissue Antigens 69:19–27. doi:10.1111/j.1399-0039.2006.00701.x
14. Prado-Garcia H, Romero-Garcia S, Morales-Fuentes J, Aguilar-Cazares D, Lopez-Gonzalez JS (2012) Activation-induced cell death of memory CD8+ T cells from pleural effusion of lung cancer patients is mediated by the type II Fas-induced apoptotic pathway. Cancer Immunol Immunother 61:1065–1080. doi:10.1007/s00262-011-1165-5
15. McMahan RH, Golden-Mason L, Nishimura MI, McMahon BJ, Kemper M, Allen TM, Gretch DR, Rosen HR (2010) Tim-3 expression on PD-1+ HCV-specific human CTLs is associated with viral persistence, and its blockade restores hepatocyte-directed in vitro cytotoxicity. J Clin Invest 120:4546–4557. doi:10.1172/jci43127
16. Noman MZ, Desantis G, Janji B, Hasmim M, Karray S, Dessen P, Bronte V, Chouaib S (2014) PD-L1 is a novel direct target of HIF-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med 211:781–790. doi:10.1084/jem.20131916
17. White AM, Wraith DC (2016) Tr1-like T cells—an enigmatic regulatory T cell lineage. Front Immunol 7:355. doi:10.3389/fimmu.2016.00355
18. Kern F, Bunde T, Faulhaber N et al (2002) Cytomegalovirus (CMV) phosphoprotein 65 makes a large contribution to shaping the T cell repertoire in CMV-exposed individuals. J Infect Dis 185:1709–1716. doi:10.1086/340637
19. Appay V, van Lier RA, Sallusto F, Roederer M (2008) Phenotype and function of human T lymphocyte subsets: consensus and issues. Cytometry A 73:975–983. doi:10.1002/cyto.a.20643
20. Brahmer JR, Tykodi SS, Chow LQ et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465. doi:10.1056/NEJMoa1200694
21. Reck M, Rodriguez-Abreu D, Robinson AG et al (2016) Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 375:1823–1833. doi:10.1056/NEJMoa1606774
22. Barsoum IB, Smallwood CA, Siemens DR, Graham CH (2014) A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells. Cancer Res 74:665–674. doi:10.1158/0008-5472.can-13-0992
23. Abiko K, Matsumura N, Hamanishi J et al (2015) IFN-gamma from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer. Br J Cancer 112:1501–1509. doi:10.1038/bjc.2015.101
24. Zhang Y, Ertl HC (2016) Starved and Asphyxiated: how can CD8+ T Cells within a tumor microenvironment prevent tumor progression. Front Immunol 7:32. doi:10.3389/fimmu.2016.00032 (eCollection 2016)
25. Roman J, Rangasamy T, Guo J et al (2010) T-cell activation under hypoxic conditions enhances IFN-gamma secretion. Am J Respir Cell Mol Biol 42:123–128. doi:10.1165/rcmb.2008-0139OC
26. Zippelius A, Schreiner J, Herzig P, Muller P (2015) Induced PD-L1 expression mediates acquired resistance to agonistic anti-CD40 treatment. Cancer Immunol Res 3:236–244. doi:10.1158/2326-6066.cir-14-0226
27. Zhang Y, Huang S, Gong D, Qin Y, Shen Q (2010) Programmed death-1 upregulation is correlated with dysfunction of tumor-infiltrating CD8+ T lymphocytes in human non-small cell lung cancer. Cell Mol Immunol 7:389–395. doi:10.1038/cmi.2010.28
28. Thommen DS, Schreiner J, Muller P et al (2015) Progression of lung cancer is associated with increased dysfunction of T cells defined by coexpression of multiple inhibitory receptors. Cancer Immunol Res 3:1344–1355. doi:10.1158/2326-6066.CIR-15-0097
29. Yin W, Tong ZH, Cui A, Zhang JC, Ye ZJ, Yuan ML, Zhou Q, Shi HZ (2014) PD-1/PD-Ls pathways between CD4(+) T cells and pleural mesothelial cells in human tuberculous pleurisy. Tuberculosis (Edinb) 94:131–139. doi:10.1016/j.tube.2013.10.007
30. Prado-Garcia H, Romero-Garcia S, Rumbo-Nava U, Lopez-Gonzalez JS (2015) Predominance of Th17 over regulatory T-cells in pleural effusions of patients with lung cancer implicates a proinflammatory profile. Anticancer Res 35:1529–1535
31. Gao X, Zhu Y, Li G et al (2012) TIM-3 expression characterizes regulatory T cells in tumor tissues and is associated with lung cancer progression. PLoS One 7:e30676. doi:10.1371/journal.pone.0030676
32. Wolfl M, Kuball J, Ho WY, Nguyen H, Manley TJ, Bleakley M, Greenberg PD (2007) Activation-induced expression of CD137 permits detection, isolation, and expansion of the full repertoire of CD8+ T cells responding to antigen without requiring knowledge of epitope specificities. Blood 110:201–210. doi:10.1182/blood-2006-11-056168
33. Haymaker C, Wu R, Bernatchez C, Radvanyi L (2012) PD-1 and BTLA and CD8(+) T-cell “exhaustion” in cancer: “exercising” an alternative viewpoint. Oncoimmunology 1:735–738. doi:10.4161/onci.20823