Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumorinfiltrating lymphocytes in ovarian high grade serous carcinoma

Oncotarget

Volumn 7, Issue 2, 2016, Pages 1486-1499

  Darb Esfahani, Silvia ^a   Kunze, Catarina Alisa ^a   Kulbe, Hagen ^a   Sehouli, Jalid ^a   Wienert, Stephan ^a,b   Lindner, Judith ^a   Budczies, Jan ^a   Bockmayr, Michael ^a   Dietel, Manfred ^a   Denkert, Carsten ^a   Braicu, Ioana ^a   Jöhrens, Korinna ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b VMSCOPE GMBH   (Germany)

Author keywords

High grade serous carcinoma; Ovarian; PD 1; PD L1; Tumor infiltrating lymphocytes

Indexed keywords

CD3 ANTIGEN; CD4 ANTIGEN; CD8 ANTIGEN; MESSENGER RNA; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 RECEPTOR; CD274 PROTEIN, HUMAN; PDCD1 PROTEIN, HUMAN; TUMOR MARKER;

ADULT; ARTICLE; CANCER GRADING; CANCER PROGNOSIS; CANCER SURVIVAL; COMPUTER MODEL; CONTROLLED STUDY; FEMALE; GENE; GENE EXPRESSION; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; IMMUNOMODULATION; MAJOR CLINICAL STUDY; MIDDLE AGED; OVARIAN CANCER CELL LINE; OVARY CARCINOMA; OVERALL SURVIVAL; PD 1 GENE; PD L1 GENE; PREDICTIVE VALUE; PROGRESSION FREE SURVIVAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SURVIVAL PREDICTION; TISSUE MICROARRAY; TUMOR ASSOCIATED LEUKOCYTE; CARCINOMA; CHEMISTRY; DISEASE FREE SURVIVAL; GENE EXPRESSION REGULATION; GENETIC DATABASE; GENETICS; IMMUNOLOGY; KAPLAN MEIER METHOD; NEOPLASMS, CYSTIC, MUCINOUS, AND SEROUS; OVARIAN NEOPLASMS; PATHOLOGY; TIME FACTOR;

ANTIGENS, CD274; BIOMARKERS, TUMOR; CARCINOMA; DATABASES, GENETIC; DISEASE-FREE SURVIVAL; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; IMMUNOHISTOCHEMISTRY; KAPLAN-MEIER ESTIMATE; LYMPHOCYTES, TUMOR-INFILTRATING; MIDDLE AGED; NEOPLASM GRADING; NEOPLASMS, CYSTIC, MUCINOUS, AND SEROUS; OVARIAN NEOPLASMS; PROGRAMMED CELL DEATH 1 RECEPTOR; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; TIME FACTORS; TISSUE ARRAY ANALYSIS;

EID: 84957667954     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.6429     Document Type: Article

References (44)

1. Bachmayr-Heyda A, Aust S, Heinze G, Polterauer S, Grimm C, Braicu EI, Sehouli J, Lambrechts S, Vergote I, Mahner S, Pils D, Schuster E, Thalhammer T, et al. Prognostic impact of tumor infiltrating CD8+ T cells in association with cell proliferation in ovarian cancer patients-a study of the OVCAD consortium. BMC Cancer. 2013; 13: 422.
2. Clarke B, Tinker AV, Lee CH, Subramanian S, van de Rijn M, Turbin D, Kalloger S, Han G, Ceballos K, Cadungog MG, Huntsman DG, Coukos G, Gilks CB. Intraepithelial T cells and prognosis in ovarian carcinoma: novel associations with stage, tumor type, and BRCA1 loss. Mod Pathol. 2009; 22: 393-402.
3. Webb JR, Milne K, Watson P, Deleeuw RJ, Nelson BH. Tumor-infiltrating lymphocytes expressing the tissue resident memory marker CD103 are associated with increased survival in high-grade serous ovarian cancer. Clin Cancer Res. 2014; 20: 434-44.
4. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 12: 252-64.
5. Topalian SL, Drake CG, Pardoll DM. Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy. Cancer Cell. 2015; 27: 450-461.
6. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000; 192: 1027-34.
7. Abdel-Magid AF. Inhibitors of the PD-1/PD-L1 Pathway Can Mobilize the Immune System: An Innovative Potential Therapy for Cancer and Chronic Infections. ACS Med Chem Lett. 2015 ;6: 489-90.
8. Ikebuchi R, Konnai S, Okagawa T, Yokoyama K, Nakajima C, Suzuki Y, Murata S, Ohashi K. Influence of PD-L1 cross-linking on cell death in PD-L1-expressing cell lines and bovine lymphocytes. Immunology. 2014; 142: 551-61.
9. Disis ML, Patel MR, Pant S, Infante JR, Lockhart A, Kelly AK, Beck JT, Gordon MS, Weiss GJ, Ejadi S, Taylor MH, von Heydebreck A, Chin KM, et al. Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with previously treated, recurrent or refractory ovarian cancer: A phase Ib, open-label expansion trial. ASCO Annual Meeting 2015 (Abstract #5509)
10. Varga A, Piha-Paul SA, Ott PA, Mehnert JM, Berton-Rigaud D, Johnson EA, Cheng JD, Yuan S, Rubin EH, Matei DE. Antitumor activity and safety of pembrolizumab in patients (pts) with PD-L1 positive advanced ovarian cancer: Interim results from a phase Ib study. ASCO Annual Meeting 2015 (#Abstract 5510)
11. Romano E, Romero P. The therapeutic promise of disrupting the PD-1/PD-L1 immune checkpoint in cancer:unleashing the CD8 T cell mediated anti-tumor activity results in significant, unprecedented clinical efficacy in various solid tumors. J Immunother Cancer. 2015; 3: 15.
12. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, Miller ML, Rekhtman N, Moreira AL, Ibrahim F, Bruggeman C, Gasmi B, Zappasodi R, Maeda Y, Sander C, Garon EB, Merghoub T, Wolchok JD, Schumacher TN, Chan TA. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015; 348: 124-8.
13. Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, West AN, Carmona M, Kivork C, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014; 515: 568-71.
14. Webb JR, Milne K, Nelson BH. PD-1 and CD103 are widely co-expressed on prognostically favorable intraepithelial CD8 T cells in human ovarian cancer. Cancer Immunol Res. 2015 [Epub ahead of print]
15. Bellmunt J, Mullane SA, Werner L, Fay AP, Callea M, Leow JJ, Taplin ME, Choueiri TK, Hodi FS, Freeman GJ, Signoretti S. Association of PD-L1 expression on tumorinfiltrating mononuclear cells and overall survival in patients with urothelial carcinoma. Ann Oncol. 2015; 26: 812-7.
16. 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: 667-76.
17. Badoual C, Hans S, Merillon N, Van Ryswick C, Ravel P, Benhamouda N, Levionnois E, Nizard M, Si-Mohamed A, Besnier N, Gey A, Rotem-Yehudar R, Pere H, et al. PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer. Cancer Res. 2013; 73: 128-38.
18. Thompson RH, Dong H, Lohse CM, Leibovich BC, Blute ML, Cheville JC, Kwon ED. PD-1 is expressed by tumorinfiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. Clin Cancer Res. 2007; 13: 1757-61.
19. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013;19:1423-37.
20. Pohla H, Buchner A, Stadlbauer B, Frankenberger B, Stevanovic S, Walter S, Frank R, Schwachula T, Olek S, Kopp J, Willimsky G, Stief CG, Hofstetter A, Pezzutto A, Blankenstein T, Oberneder R, Schendel DJ. High immune response rates and decreased frequencies of regulatory T cells in metastatic renal cell carcinoma patients after tumor cell vaccination. Mol Med. 2013; 18: 1499-508.
21. Liao Y, Wang B, Huang ZL, Shi M, Yu XJ, Zheng L, Li S, Li L. Increased circulating Th17 cells after transarterial chemoembolization correlate with improved survival in stage III hepatocellular carcinoma: a prospective study. PLoS One. 2013; 8: e60444.
22. γδd T cells that recognize phosphoantigens. Eur J Immunol. 2011;41:345-55.
23. Iwamura K, Kato T, Miyahara Y, Naota H, Mineno J, Ikeda H, Shiku H. siRNA-mediated silencing of PD-1 ligands enhances tumor-specific human T-cell effector functions. Gene Ther. 2012;19(10):959-66.
24. Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348:203-13.
25. Raspollini MR, Castiglione F, Rossi Degl'innocenti D, Amunni G, Villanucci A, Garbini F, Baroni G, Taddei GL. Tumour-infiltrating gamma/delta T-lymphocytes are correlated with a brief disease-free interval in advanced ovarian serous carcinoma. Ann Oncol. 2005;16:590-6.
26. Zhang Y, Kang S, Shen J, He J, Jiang L, Wang W, Guo Z, Peng G, Chen G, He J, Liang W. Prognostic significance of programmed cell death 1 (PD-1) or PD-1 ligand 1 (PD-L1) Expression in epithelial-originated cancer: a meta-analysis. Medicine (Baltimore). 2015; 94: e515.
27. Lussier DM, Johnson JL, Hingorani P, Blattman JN. Combination immunotherapy with a-CTLA-4 and a-PD-L1 antibody blockade prevents immune escape and leads to complete control of metastatic osteosarcoma. J Immunother Cancer. 2015; 3:21.
28. Tjin EP, Krebbers G, Meijlink KJ, van de Kasteele W, Rosenberg EH, Sanders J, Nederlof PM, van de Wiel BA, Haanen JB, Melief CJ, Vyth-Dreese FA, Luiten RM. Immune-escape markers in relation to clinical outcome of advanced melanoma patients following immunotherapy. Cancer Immunol Res. 2014; 2: 538-46.
29. Schmidt LH, Kümmel A, Görlich D, Mohr M, Bröckling S, Mikesch JH, Grünewald I, Marra A, Schultheis AM, Wardelmann E, Müller-Tidow C, Spieker T, Schliemann C, Berdel WE, Wiewrodt R, Hartmann W.PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups. PLoS One. 2015;10:e0136023.
30. Kluger HM, Zito CR, Barr ML, Baine MK, Chiang VL, Sznol M, Rimm DL, Chen L, Jilaveanu LB. Characterization of PD-L1 Expression and Associated T-cell Infiltrates in Metastatic Melanoma Samples from Variable Anatomic Sites. Clin Cancer Res. 2015;21:3052-60.
31. Hamanishi J, Mandai M, Iwasaki M, Okazaki T, Tanaka Y, Yamaguchi K, Higuchi T, Yagi H, Takakura K, Minato N, Honjo T, Fujii S. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci U S A. 2007; 104: 3360-5.
32. Ali HR, Glont SE, Blows FM, Provenzano E, Dawson SJ, Liu B, Hiller L, Dunn J, Poole CJ, Bowden S, Earl HM, Pharoah PD, Caldas C. PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes. Ann Oncol. 2015 [Epub ahead of print].
33. Schalper KA, Velcheti V, Carvajal D, Wimberly H, Brown J, Pusztai L, Rimm DL. In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas. Clin Cancer Res. 2014; 20: 2773-82.
34. Gettinger SN, Horn L, Gandhi L, Spigel DR, Antonia SJ, Rizvi NA, Powderly JD, Heist RS, Carvajal RD, Jackman DM, Sequist LV, Smith DC, Leming P, et al. Overall Survival and Long-Term Safety of Nivolumab (Anti-Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2015;33:2004-12.
35. McDermott DF, Drake CG, Sznol M, Choueiri TK, Powderly JD, Smith DC, Brahmer JR, Carvajal RD, Hammers HJ, Puzanov I, Hodi FS, Kluger HM, Topalian SL, et al. Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab. J Clin Oncol. 2015;33:2013-20.
36. D'Incecco A, Andreozzi M, Ludovini V, Rossi E, Capodanno A, Landi L, Tibaldi C, Minuti G, Salvini J, Coppi E, Chella A, Fontanini G, Filice ME, et al. PD-1 and PD-L1 expression in molecularly selected non-small-cell lung cancer patients. Br J Cancer. 2015; 112: 95-102.
37. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, et al. KEYNOTE-001Investigators. Pembrolizumab for the Treatment of Non-Small-Cell Lung Cancer. N Engl J Med. 2015; 372: 2018-2028.
38. Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, Bellmunt J, Burris HA, Petrylak DP, Teng SL, Shen X, Boyd Z, Hegde PS, Chen DS, Vogelzang NJ. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014; 515: 558-62.
39. Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN, Kohrt HE, Horn L, Lawrence DP, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014; 515: 563-7.
40. Darb-Esfahani S, Sinn BV, Weichert W, Budczies J, Lehmann A, Noske A, Buckendahl AC, Müller BM, Sehouli J, Koensgen D, Györffy B, Dietel M, Denkert C. Expression of classical NF-kappaB pathway effectors in human ovarian carcinoma. Histopathology. 2010. 56: 727-39.
41. Wienert S, Heim D, Kotani M, Lindequist B, Stenzinger A, Ishii M, Hufnagl P, Beil M, Dietel M, Denkert C, Klauschen F. CognitionMaster: an object-based image analysis framework. Diagn Pathol. 2013; 8:34.
42. Denkert C, von Minckwitz G, Brase JC, Sinn BV, Gade S, Kronenwett R, Pfitzner BM, Salat C, Loi S, Schmitt WD, Schem C, Fisch K, Darb-Esfahani S, et al. Tumorinfiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triplenegative primary breast cancers. J Clin Oncol. 2015; 33: 983-91.
43. Budczies J, Klauschen F, Sinn BV, Gyorffy B, Schmitt WD, Darb-Esfahani S, Denkert C. CutoffFinder: a comprehensive and straightforward Web application enabling rapid biomarker cutoffoptimization. PLoS One. 2012;7:e51862.
44. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474:609-15.