PD-L1 and PD-1 and characterization of tumor-infiltrating lymphocytes in high grade sarcomas of soft tissue – prognostic implications and rationale for immunotherapy

References

• Christopher D, Fletcher JA, Krishnan U. WHO classification of tumours of soft tissue and bone. International agency for research on cancer 4th edition Lyon; 2013:110–1.
   Google Scholar
• Brennan MF, Antonescu CR, Maki RG. Management of soft tissue sarcoma. New York: Springer; 2013.
   Google Scholar
• Stiller CA, Trama A, Serraino D, Rossi S, Navarro C, Chirlaque MD, Casali PG, RARECARE Working Group. Descriptive epidemiology of sarcomas in Europe: report from the RARECARE project. Eur J Cancer. 2013;49:684–95. doi:10.1016/j.ejca.2012.09.011. PMID:23079473.
   PubMed Web of Science ®Google Scholar
• Sant M, Allemani C, Santaquilani M, Knijn A, Marchesi F, Capocaccia R, EUROCARE Working Group. EUROCARE-4. Survival of cancer patients diagnosed in 1995–1999. Results and commentary. Eur J Cancer. 2009;45:931–91. doi:10.1016/j.ejca.2008.11.018. PMID:19171476.
   PubMed Web of Science ®Google Scholar
• Maretty-Nielsen K, Aggerholm-Pedersen N, Safwat A, Jorgensen PH, Hansen BH, Baerentzen S, Pedersen AB, Keller J. Prognostic factors for local recurrence and mortality in adult soft tissue sarcoma of the extremities and trunk wall: a cohort study of 922 consecutive patients. Acta Orthop. 2014;85:323–32. doi:10.3109/17453674.2014.908341. PMID:24694277.
   PubMed Web of Science ®Google Scholar
• Teng MW, Ngiow SF, Ribas A, Smyth MJ. Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res. 2015;75:2139–45. doi:10.1158/0008-5472.CAN-15-0255. PMID:25977340.
   PubMed Web of Science ®Google Scholar
• Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther. 2015;14:847–56. doi:10.1158/1535-7163.MCT-14-0983. PMID:25695955.
   PubMed Web of Science ®Google Scholar
• Spranger S. Mechanisms of tumor escape in the context of the T-cell-inflamed and the non-T-cell-inflamed tumor microenvironment. Int Immunol. 2016;28:383–91. doi:10.1093/intimm/dxw014. PMID:26989092.
   PubMed Web of Science ®Google Scholar
• Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541:321–30. doi:10.1038/nature21349. PMID:28102259.
   PubMed Web of Science ®Google Scholar
• Kim C, Kim EK, Jung H, Chon HJ, Han JW, Shin KH, Hu H, Kim KS, Choi YD, Kim S, et al. Prognostic implications of PD-L1 expression in patients with soft tissue sarcoma. BMC Cancer. 2016;16:434. doi:10.1186/s12885-016-2451-6. PMID:27393385.
   PubMed Web of Science ®Google Scholar
• D'Angelo SP, Shoushtari AN, Agaram NP, Kuk D, Qin LX, Carvajal RD, Dickson MA, Gounder M, Keohan ML, Schwartz GK, et al. Prevalence of tumor-infiltrating lymphocytes and PD-L1 expression in the soft tissue sarcoma microenvironment. Hum Pathol. 2015;46:357–65. doi:10.1016/j.humpath.2014.11.001. PMID:25540867.
   PubMed Web of Science ®Google Scholar
• Tseng WW, Malu S, Zhang M, Chen J, Sim GC, Wei W, Ingram D, Somaiah N, Lev DC, Pollock RE, et al. Analysis of the intratumoral adaptive immune response in well differentiated and dedifferentiated retroperitoneal liposarcoma. Sarcoma. 2015;2015:547460. doi:10.1155/2015/547460. PMID:25705114.
   PubMedGoogle Scholar
• Paydas S, Bagir EK, Deveci MA, Gonlusen G. Clinical and prognostic significance of PD-1 and PD-L1 expression in sarcomas. Med Oncol. 2016;33:93. doi:10.1007/s12032-016-0807-z. PMID:27421997.
   PubMed Web of Science ®Google Scholar
• Kim JR, Moon YJ, Kwon KS, Bae JS, Wagle S, Kim KM, Park HS, Lee H, Moon WS, Chung MJ, et al. Tumor infiltrating PD1-positive lymphocytes and the expression of PD-L1 predict poor prognosis of soft tissue sarcomas. PLoS One. 2013;8:e82870. doi:10.1371/journal.pone.0082870. PMID:24349382.
   PubMed Web of Science ®Google Scholar
• Sorbye SW, Kilvaer T, Valkov A, Donnem T, Smeland E, Al-Shibli K, Bremnes RM, Busund LT. High expression of CD20+ lymphocytes in soft tissue sarcomas is a positive prognostic indicator. Oncoimmunology. 2012;1:75–7. doi:10.4161/onci.1.1.17825. PMID:22720216.
   PubMed Web of Science ®Google Scholar
• Tseng WW, Somaiah N, Engleman EG. Potential for immunotherapy in soft tissue sarcoma. Hum Vaccin Immunother. 2014;10:3117–24. doi:10.4161/21645515.2014.983003. PMID:25625925.
   PubMed Web of Science ®Google Scholar
• Tawbi HA, Burgess M, Bolejack V, Van Tine BA, Schuetze SM, Hu J, D'Angelo S, Attia S, Riedel RF, Priebat DA, et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. The Lancet Oncology. 2017.
   Google Scholar
• Galon J, Pages F, Marincola FM, Angell HK, Thurin M, Lugli A, Zlobec I, Berger A, Bifulco C, Botti G, et al. Cancer classification using the Immunoscore: a worldwide task force. J Transl Med. 2012;10:205. doi:10.1186/1479-5876-10-205. PMID:23034130.
   PubMed Web of Science ®Google Scholar
• Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, Lugli A, Zlobec I, Hartmann A, Bifulco C, et al. Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol. 2014;232:199–209. doi:10.1002/path.4287. PMID:24122236.
   PubMed Web of Science ®Google Scholar
• Galon J, Fox BA, Bifulco CB, Masucci G, Rau T, Botti G, Marincola FM, Ciliberto G, Pages F, Ascierto PA, et al. Immunoscore and Immunoprofiling in cancer: an update from the melanoma and immunotherapy bridge 2015. J Transl Med. 2016;14:273. doi:10.1186/s12967-016-1029-z.
   PubMed Web of Science ®Google Scholar
• Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39:1–10. doi:10.1016/j.immuni.2013.07.012. PMID:23890059.
   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 T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med. 2013;5:200ra116. doi:10.1126/scitranslmed.3006504. PMID:23986400.
   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. doi:10.1126/scitranslmed.3003689. PMID:22461641.
   PubMed Web of Science ®Google Scholar
• Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, 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. doi:10.1084/jem.192.7.1027. PMID:11015443.
   PubMed Web of Science ®Google Scholar
• Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515:568–71. doi:10.1038/nature13954. PMID:25428505.
   PubMed Web of Science ®Google Scholar
• Green MR, Monti S, Rodig SJ, Juszczynski P, Currie T, O'Donnell E, Chapuy B, Takeyama K, Neuberg D, Golub TR, et al. Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood. 2010;116:3268–77. doi:10.1182/blood-2010-05-282780. PMID:20628145.
   PubMed Web of Science ®Google Scholar
• Barrett MT, Anderson KS, Lenkiewicz E, Andreozzi M, Cunliffe HE, Klassen CL, Dueck AC, McCullough AE, Reddy SK, Ramanathan RK, et al. Genomic amplification of 9p24.1 targeting JAK2, PD-L1, and PD-L2 is enriched in high-risk triple negative breast cancer. Oncotarget. 2015;6:26483–93. doi:10.18632/oncotarget.4494. PMID:26317899.
   PubMed Web of Science ®Google Scholar
• Straub M, Drecoll E, Pfarr N, Weichert W, Langer R, Hapfelmeier A, Götz C, Wolff KD, Kolk A, Specht K. CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity. Oncotarget. 2016;7:12024–34. doi:10.18632/oncotarget.7593. PMID:26918453.
   PubMed Web of Science ®Google Scholar
• Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–64. doi:10.1038/nrc3239. PMID:22437870.
   PubMed Web of Science ®Google Scholar
• Parsa AT, Waldron JS, Panner A, Crane CA, Parney IF, Barry JJ, Cachola KE, Murray JC, Tihan T, Jensen MC, et al. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med. 2007;13:84–8. doi:10.1038/nm1517. PMID:17159987.
   PubMed Web of Science ®Google Scholar
• Wang X, Teng F, Kong L, Yu J. PD-L1 expression in human cancers and its association with clinical outcomes. Onco Targets Ther. 2016;9:5023–39. doi:10.2147/OTT.S105862. PMID:27574444.
   PubMed Web of Science ®Google Scholar
• Gooden MJ, de Bock GH, Leffers N, Daemen T, Nijman HW. The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br J Cancer. 2011;105:93–103. doi:10.1038/bjc.2011.189. PMID:21629244.
   PubMed Web of Science ®Google Scholar
• Movva S, Wen W, Chen W, Millis SZ, Gatalica Z, Reddy S, von Mehren M, Van Tine BA. Multi-platform profiling of over 2000 sarcomas: identification of biomarkers and novel therapeutic targets. Oncotarget. 2015;6:12234–47. doi:10.18632/oncotarget.3498. PMID:25906748.
   PubMed Web of Science ®Google Scholar
• Gandhi L, Balmanoukian A, Hui R, Hamid O, Rizvi NA, Leighl N, Gubens M, Goldman JW, Lubiniecki GM, Emancipator K, et al. Abstract CT105: MK-3475 (anti-PD-1 monoclonal antibody) for non-small cell lung cancer (NSCLC): Antitumor activity and association with tumor PD-L1 expression. Cancer Research. 2014;74:CT105–CT. doi:10.1158/1538-7445.AM2014-CT105.
   Web of Science ®Google Scholar
• Gettinger SN, Shepherd FA, Antonia SJ, Brahmer JR, Chow LQM, Juergens RA, Borghaei H, Shen Y, Harbison C, Alaparthy S, et al. First-line nivolumab (anti-PD-1; BMS-936558, ONO-4538) monotherapy in advanced NSCLC: Safety, efficacy, and correlation of outcomes with PD-L1 status. ASCO Annual Meeting Proceedings; 2014:8024.
   Google Scholar
• Grosso J, Horak CE, Inzunza D, Cardona DM, Simon JS, Gupta AK, Sankar V, Park JS, Kollia G, Taube JM, et al. Association of tumor PD-L1 expression and immune biomarkers with clinical activity in patients (pts) with advanced solid tumors treated with nivolumab (anti-PD-1; BMS-936558; ONO-4538). ASCO Annual Meeting Proceedings; 2013:3016.
   Google Scholar
• Hodi FS, Sznol M, Kluger HM, McDermott DF, Carvajal RD, Lawrence DP, Topalian SL, Atkins MB, Powderly JD, Sharfman WH, et al. Long-term survival of ipilimumab-naive patients (pts) with advanced melanoma (MEL) treated with nivolumab (anti-PD-1, BMS-936558, ONO-4538) in a phase I trial. ASCO Annual Meeting Proceedings; 2014:9002.
   Google Scholar
• Kefford R, Ribas A, Hamid O, Robert C, Daud A, Wolchok JD, Joshua AM, Hodi FS, Gangadhar TC, Hersey P, et al. Clinical efficacy and correlation with tumor PD-L1 expression in patients (pts) with melanoma (MEL) treated with the anti-PD-1 monoclonal antibody MK-3475. ASCO Annual Meeting Proceedings; 2014:3005.
   Google Scholar
• Grigg C, Rizvi NA. PD-L1 biomarker testing for non-small cell lung cancer: truth or fiction? J Immunother Cancer. 2016;4:48. doi:10.1186/s40425-016-0153-x. PMID:27532023.
   PubMed Web of Science ®Google Scholar
• Rizvi NA, Brahmer JR, Ou S-HI, Segal NH, Khleif S, Hwu W-J, Gutierrez M, Schoffski P, Hamid O, Weiss J, et al. Safety and clinical activity of MEDI4736, an anti-programmed cell death-ligand 1 (PD-L1) antibody, in patients with non-small cell lung cancer (NSCLC). American Society of Clinical Oncology; 2015.
   Google Scholar
• de Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer. 2006;6:24–37. doi:10.1038/nrc1782. PMID:16397525.
   PubMed Web of Science ®Google Scholar
• Sorbye SW, Kilvaer TK, Valkov A, Donnem T, Smeland E, Al-Shibli K, Bremnes RM, Busund LT. Prognostic impact of peritumoral lymphocyte infiltration in soft tissue sarcomas. BMC Clin Pathol. 2012;12:5. doi:10.1186/1472-6890-12-5. PMID:22375962.
   PubMedGoogle Scholar
• Fujii H, Arakawa A, Utsumi D, Sumiyoshi S, Yamamoto Y, Kitoh A, Ono M, Matsumura Y, Kato M, Konishi K, et al. CD8(+) tumor-infiltrating lymphocytes at primary sites as a possible prognostic factor of cutaneous angiosarcoma. Int J Cancer. 2014;134:2393–402. doi:10.1002/ijc.28581. PMID:24243586.
   PubMed Web of Science ®Google Scholar
• Botti G, Scognamiglio G, Cantile M. PD-L1 immunohistochemical detection in tumor cells and tumor microenvironment: main considerations on the use of tissue micro arrays. Int J Mol Sci. 2016;17.
   Web of Science ®Google Scholar
• Dislich B, Stein A, Seiler CA, Kroll D, Berezowska S, Zlobec I, Galvan J, Slotta-Huspenina J, Walch A, Langer R. Expression patterns of programmed death-ligand 1 in esophageal adenocarcinomas: comparison between primary tumors and metastases. Cancer Immunol Immunother. 2017;66:777–86. doi:10.1007/s00262-017-1982-2. PMID:28289861.
   PubMed Web of Science ®Google Scholar
• Guillou L, Coindre J-M, Bonichon F, Nguyen B, Terrier P, Collin F, Vilain MO, Mandard AM, Le Doussal V, Leroux A, et al. Comparative study of the national cancer institute and french federation of cancer centers sarcoma group grading systems in a population of 410 adult patients with soft tissue sarcoma. J Clin Oncol. 1997;15:350–62. doi:10.1200/JCO.1997.15.1.350. PMID:8996162.
   PubMed Web of Science ®Google Scholar
• Wittekind C. [2010 TNM system: on the 7th edition of TNM classification of malignant tumors]. Pathologe. 2010;31:331–2. doi:10.1007/s00292-010-1349-3. PMID:20703480.
   PubMed Web of Science ®Google Scholar
• Schildhaus HU, Heukamp LC, Merkelbach-Bruse S, Riesner K, Schmitz K, Binot E, Paggen E, Albus K, Schulte W, Ko YD, et al. Definition of a fluorescence in-situ hybridization score identifies high- and low-level FGFR1 amplification types in squamous cell lung cancer. Mod Pathol. 2012;25:1473–80. doi:10.1038/modpathol.2012.102. PMID:22684217.
   PubMed Web of Science ®Google Scholar