PD-L1 (CD274) copy number gain, expression, and immune cell infiltration as candidate predictors for response to immune checkpoint inhibitors in soft-tissue sarcoma

OncoImmunology

Volumn 6, Issue 3, 2017, Pages

  Budczies, Jan ^a,b   Mechtersheimer, Gunhild ^c   Denkert, Carsten ^a,b   Klauschen, Frederick ^a   Mughal, Sadaf S ^b   Chudasama, Priya ^b   Bockmayr, Michael ^a   Jöhrens, Korinna ^a   Endris, Volker ^c   Lier, Amelie ^c   Lasitschka, Felix ^c   Penzel, Roland ^c   Dietel, Manfred ^a,b   Brors, Benedikt ^b   Gröschel, Stefan ^b,c   Glimm, Hanno ^b,c   Schirmacher, Peter ^b,c   Renner, Marcus ^c   Fröhling, Stefan ^b,c   Stenzinger, Albrecht ^b,c  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^c UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

Author keywords

Amplification; CD274; immune checkpoint inhibition; PD L1; soft tissue sarcoma

Indexed keywords

CHECKPOINT KINASE INHIBITOR; JANUS KINASE 2; PEMBROLIZUMAB; PROGRAMMED DEATH 1 LIGAND 1;

ARTICLE; CD4 CD8 RATIO; CELL INFILTRATION; CONTROLLED STUDY; COPY NUMBER VARIATION; DEDIFFERENTIATED LIPOSARCOMA; DESMOID TUMOR; DISEASE FREE SURVIVAL; FLUORESCENCE IN SITU HYBRIDIZATION; GENE DOSAGE; GENE EXPRESSION; HUMAN; HUMAN TISSUE; IMMUNE RESPONSE; IMMUNOHISTOCHEMISTRY; LEIOMYOSARCOMA; LUNG ADENOCARCINOMA; MAJOR CLINICAL STUDY; MALIGNANT PERIPHERAL NERVE SHEATH TUMOR; MICROARRAY ANALYSIS; MRNA EXPRESSION ASSAY; MUTATIONAL LOAD; MYXOFIBROSARCOMA; OVERALL SURVIVAL; PROTEIN EXPRESSION; RNA SEQUENCE; SIGNAL TRANSDUCTION; SOFT TISSUE SARCOMA; SOMATIC MUTATION; SURVIVAL ANALYSIS;

EID: 85014516791     PISSN: 21624011     EISSN: 2162402X     Source Type: Journal    
DOI: 10.1080/2162402X.2017.1279777     Document Type: Article

References (56)

1. Fletcher CD, Hogendoorn P, Mertens F, Bridge J. WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. Lyon, France:IARC Press, 2013
2. Brooks JS, Lee S. Contemporary diagnostics:sarcoma pathology update. J Surg Oncol 2015; 111:513-9; PMID:25689920; http://dx.doi.org/10.1002/jso.23853
3. Ducimetière F, Lurkin A, Ranchère-Vince D, Decouvelaere AV, Péoc'h M, Istier L, Chalabreysse P, Muller C, Alberti L, Bringuier PP, et al. Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing. PLoS One 2011; 6:e20294; PMID:21826194; http://dx.doi.org/10.1371/journal.pone.0020294
4. Karavasilis V, Seddon BM, Ashley S, Al-Muderis O, Fisher C, Judson I. Significant clinical benefit of first-line palliative chemotherapy in advanced soft-tissue sarcoma:retrospective analysis and identification of prognostic factors in 488 patients. Cancer 2008; 112:1585-91; PMID:18278813; http://dx.doi.org/10.1002/cncr.23332
5. Linch M, Miah AB, Thway K, Judson IR, Benson C. Systemic treatment of soft-tissue sarcoma-gold standard and novel therapies. Nat Rev Clin Oncol 2014; 11:187-202; PMID:24642677; http://dx.doi.org/10.1038/nrclinonc.2014.26
6. Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, Issels R, van Oosterom A, Hogendoorn PC, Van Glabbeke M, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib:randomised trial. Lancet 2004; 364:1127-34; PMID:15451219; http://dx.doi.org/10.1016/S0140-6736(04)17098-0
7. Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, Raymond AK, Bramwell VH, Baker LH, Maki RG, et al. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase:S0033. J Clin Oncol 2008;26:626-32; PMID:18235122; http://dx.doi.org/10.1200/JCO.2007.13.4452
8. Rosenberg SA, Lotze MT, Yang JC, Aebersold PM, Linehan WM, Seipp CA, White DE. Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients. Ann Surg 1989; 210:474-84; PMID:2679456; http://dx.doi.org/10.1097/00000658-198910000-00008
9. Rosenberg SA. IL-2:the first effective immunotherapy for human cancer. J Immunol 2014; 192:5451-8; PMID:24907378; http://dx.doi.org/10.4049/jimmunol.1490019
10. Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science 2015; 348:62-8; PMID:25838374; http://dx.doi.org/10.1126/science.aaa4967
11. Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, Wunderlich JR, Nahvi AV, Helman LJ, Mackall CL, et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol 2011; 29:917-24; PMID:21282551; http://dx.doi.org/10.1200/JCO.2010.32.2537
12. Lipson EJ, Forde PM, Hammers HJ, Emens LA, Taube JM, Topalian SL. Antagonists of PD-1 and PD-L1 in Cancer Treatment. Semin Oncol 2015;42:587-600; PMID:26320063; http://dx.doi.org/10.1053/j.seminoncol.2015.05.013
13. Tawbi H. Safety and efficacy of PD-1 blockade using pembrolizumab in patients with advanced soft tissue (STS) and bone sarcomas (BS):Results of SARC028—A multicenter phase II study. Presented at ASCO 2016, Chicago, Abstract# 11006
14. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366:2443-54; PMID:22658127; http://dx.doi.org/10.1056/NEJMoa1200690
15. Topalian SL, Taube JM, Anders RA, Pardoll DM. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer 2016; 16:275-87; PMID:27079802; http://dx.doi.org/10.1038/nrc.2016.36
16. 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; PMID:24349382; http://dx.doi.org/10.1371/journal.pone.0082870
17. 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; PMID:25540867; http://dx.doi.org/10.1016/j.humpath.2014.11.001
18. Raj S, Bui M, Gonzales R, Letson D, Antonia SJ. Impact of PDL1 expression on clinical outcomes in subtypes of sarcoma. Ann Oncol 2014; 25 (suppl 4):iv498; http://doi.org/10.1093/annonc/mdu354.10
19. 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; PMID:25906748; http://dx.doi.org/10.18632/oncotarget.3498
20. Inoue Y, Yoshimura K, Mori K, Kurabe N, Kahyo T, Mori H, Kawase A, Tanahashi M, Ogawa H, Inui N, et al. Clinical significance of PD-L1 and PD-L2 copy number gains in non-small-cell lung cancer. Oncotarget 2016; 7:32113-28; PMID:27050074; http://dx.doi.org/10.18632/oncotarget.8528.
21. Van Roosbroeck K, Ferreiro JF, Tousseyn T, van der Krogt JA, Michaux L, Pienkowska-Grela B, Theate I, De Paepe P, Dierickx D, Doyen C, et al. Genomic alterations of the JAK2 and PDL loci occur in a broad spectrum of lymphoid malignancies. Genes Chromosomes Cancer 2016; 55:428-41; PMID:26850007; http://dx.doi.org/10.1002/gcc.22345
22. 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; PMID:26317899; http://dx.doi.org/10.18632/oncotarget.4494
23. Budczies J, Bockmayr M, Denkert C, Klauschen F, Gröschel S, Darb-Esfahani S, Pfarr N, Leichsenring J, Onozato ML, Lennerz JK, et al. Pan-cancer analysis of copy number changes in programmed death-ligand 1 (PD-L1, CD274)–associations with gene expression, mutational load, and survival. Genes Chromosomes Cancer 2016; 55:626-39; PMID:27106868; http://dx.doi.org/10.1002/gcc.22365
24. Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med 2015; 372:311-9; PMID:25482239; http://dx.doi.org/10.1056/NEJMoa1411087
25. R Core Team. 2013. R:A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL:http://www.R-project.org/
26. Jacobson A. R-Based API for Accessing the MSKCC Cancer Genomics Data Server. R package version 2015; 1.2.5. http://CRAN.R-project.org/package
27. Carlson M. Genome wide annotation for Human, primarily based on mapping using Entrez Gene identifiers. R package version 2015; 3.0.0
28. Therneau TM, Grambsch PM. Modeling Survival Data:Extending the Cox Model. USA:Springer, 2000.
29. Coindre JM. Grading of soft tissue sarcomas:review and update. Arch Pathol Lab Med 2006; 130:1448-53; PMID:17090186
30. Chudasama P, Renner M, Straub M, Mughal SS, Hutter B, Kosaloglu Z, Schweßinger R, Scheffler M, Alldinger I, Schimmack S, et al. Targeting fibroblast growth factor receptor 1 for treatment of soft-tissue sarcoma. Clin Cancer Res 2016; pii:clincanres.0860.2016; PMID:27535980; http://dx.doi.org/10.1158/1078-0432.CCR-16-0860 [Epub ahead of print]
31. Renner M, Wolf T, Meyer H, Hartmann W, Penzel R, Ulrich A, Lehner B, Hovestadt V, Czwan E, Egerer G, et al. Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas. Genome Biol 2013; 14:r137; PMID:24345474; http://dx.doi.org/10.1186/gb-2013-14-12-r137
32. Rebelatto MC, Midha A, Mistry A, Sabalos C, Schechter N, Li X, Jin X, Steele KE, Robbins PB, Blake-Haskins JA, et al. Development of a programmed cell death ligand-1 immunohistochemical assay validated for analysis of non-small cell lung cancer and head and neck squamous cell carcinoma. Diagn Pathol 2016; 11:95; PMID:27717372; http://dx.doi.org/10.1186/s13000-016-0545-8
33. Gröschel S, Bommer M, Hutter B, Budczies J, Bonekamp D, Heining C, Horak P, Fröhlich M, Uhrig S, Hübschmann D, et al. Integration of genomics and histology revises diagnosis and enables effective therapy of refractory cancer of unknown primary with PDL1 amplification. Cold Spring Harb Mol Case Stud 2016; 2:a001180; PMID:27900363; http://dx.doi.org/10.1101/mcs.a001180
34. McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelekanou V, Rehman J, Velcheti V, Herbst R, LoRusso P, Rimm DL. Quantitative assessment of the heterogeneity of PD-L1 expression in non-small-cell lung cancer. JAMA Oncol 2016; 2:46-54; PMID:26562159; http://dx.doi.org/10.1001/jamaoncol.2015.3638
35. Patel SP, Kurzrock R. PD-L1 Expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther 2015; 14:847-56; PMID:25695955; http://dx.doi.org/10.1158/1535-7163.MCT-14-0983
36. Roemer MG, Advani RH, Ligon AH, Natkunam Y, Redd RA, Homer H, Connelly CF, Sun HH, Daadi SE, Freeman GJ, et al. PD-L1 and PD-L2 genetic alterations define classical hodgkin lymphoma and predict outcome. J Clin Oncol 2016; 34(23):2690-7; PMID:27069084; http://dx.doi.org/10.1200/JCO.2016.66.4482
37. Balko JM, Schwarz LJ, Luo N, Estrada MV, Giltnane JM, Dávila-González D, Wang K, Sánchez V, Dean PT, Combs SE, et al. Triple-negative breast cancers with amplification of JAK2 at the 9p24 locus demonstrate JAK2-specific dependence. Sci Transl Med 2016; 8:334ra53; PMID:27075627; http://dx.doi.org/10.1126/scitranslmed.aad3001
38. Cheung N, Fung TK, Zeisig BB, Holmes K, Rane JK, Mowen KA, Finn MG, Lenhard B, Chan LC, So CW. Targeting aberrant epigenetic networks mediated by PRMT1 and KDM4C in acute myeloid leukemia. Cancer Cell 2016; 29:32-48; PMID:26766589; http://dx.doi.org/10.1016/j.ccell.2015.12.007
39. Kupershmit I, Khoury-Haddad H, Awwad SW, Guttmann-Raviv N, Ayoub N. KDM4C (GASC1) lysine demethylase is associated with mitotic chromatin andregulates chromosome segregation during mitosis. Nucleic Acids Res 2014; 42:6168-82; PMID:24728997; http://dx.doi.org/10.1093/nar/gku253
40. McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D, Pelekanou V, Rehman J, Velcheti V, Herbst R, LoRusso P, Rimm DL. Quantitative assessment of the heterogeneity of PD-L1 expression in non-small-cell lung cancer. JAMA Oncol 2016; 2:46-54; PMID:26562159; http://dx.doi.org/10.1001/jamaoncol.2015.3638
41. Scheel AH, Dietel M, Heukamp LC, Jöhrens K, Kirchner T, Reu S, Rüschoff J, Schildhaus HU, Schirmacher P, Tiemann M, et al. Harmonized PD-L1 immunohistochemistry for pulmonary squamous-cell and adenocarcinomas. Mod Pathol 2016; 29:1165-72; PMID:27389313; http://dx.doi.org/10.1038/modpathol.2016.117
42. Chabanon RM, Pedrero M, Lefebvre C, Marabelle A, Soria JC, Postel-Vinay S. Mutational landscape and sensitivity to immune checkpoint blockers. Clin Cancer Res 2016; 22:4309-21; PMID:27390348; http://dx.doi.org/10.1158/1078-0432.CCR-16-0903
43. Budczies J, Bockmayr M, Denkert C, Klauschen F, Lennerz JK, Györffy B, Dietel M, Loibl S, Weichert W, Stenzinger A. Classical pathology and mutational load of breast cancer–integration of two worlds. J Pathol Clin Res 2015; 1:225-38; PMID:27499907; http://dx.doi.org/10.1002/cjp2.25
44. Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 2014; 371:2189-99; PMID:25409260; http://dx.doi.org/10.1056/NEJMoa1406498
45. Van Allen EM, Miao D, Schilling B, Shukla SA, Blank C, Zimmer L, Sucker A, Hillen U, Geukes Foppen MH, Goldinger SM, et al. Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science 2015; 350:207-1; PMID:26359337; http://dx.doi.org/10.1126/science.aad0095
46. McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, Jamal-Hanjani M, Wilson GA, Birkbak NJ, Hiley CT, et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 2016; 351:1463-9; PMID:26940869; http://dx.doi.org/10.1126/science.aaf1490
47. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, et al. PD-1 Blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015; 372:2509-20; PMID:26028255; http://dx.doi.org/10.1056/NEJMoa1500596
48. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015; 348:124-8; PMID:25765070; http://dx.doi.org/10.1126/science.aaa1348
49. Nghiem PT, Bhatia S, Lipson EJ, Kudchadkar RR, Miller NJ, Annamalai L, Berry S, Chartash EK, Daud A, Fling SP, et al. PD-1 blockade with pembrolizumab in advanced merkel-cell carcinoma. N Engl J Med 2016; 374:2542-52; PMID:27093365; http://dx.doi.org/10.1056/NEJMoa1603702
50. Savas P, Salgado R, Denkert C, Sotiriou C, Darcy PK, Smyth MJ, Loi S. Clinical relevance of host immunity in breast cancer:from TILs to the clinic. Nat Rev Clin Oncol 2016; 13:228-41; PMID:26667975; http://dx.doi.org/10.1038/nrclinonc.2015.215
51. Fridman WH, Galon J, Pagès F, Tartour E, Sautès-Fridman C, Kroemer G. Prognostic and predictive impact of intra- and peritumoral immune infiltrates. Cancer Res 2011; 71:5601-5; PMID:21846822; http://dx.doi.org/10.1158/0008-5472.CAN-11-1316
52. Galon J, Pagès 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; PMID:23034130; http://dx.doi.org/10.1186/1479-5876-10-205
53. Wargo JA, Reddy SM, Reuben A, Sharma P. Monitoring immune responses in the tumor microenvironment. Curr Opin Immunol 2016; 41:23-31; PMID:27240055; http://dx.doi.org/10.1016/j.coi.2016.05.006
54. Burgess M, Tawbi H. Immunotherapeutic approaches to sarcoma. Curr Treat Options Oncol 2015; 16:26; PMID:25975445; http://dx.doi.org/10.1007/s11864-015-0345-5
55. Burgess M, Gorantla V, Weiss K, Tawbi H. Immunotherapy in sarcoma:future horizons. Curr Oncol Rep 2015; 17:52; PMID:26423769; http://dx.doi.org/10.1007/s11912-015-0476-7
56. Lee A, Huang P, DeMatteo RP, Pollack SM. Immunotherapy for soft tissue sarcoma:tomorrow is only a day away. Am Soc Clin Oncol Educ Book 2016; 35:281-90; PMID:27249707; http://dx.doi.org/10.14694/EDBK_157439