Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy

Nature Communications

Volumn 7, Issue , 2016, Pages

  Johnson, Douglas B ^a   Estrada, Monica V ^a   Salgado, Roberto ^b   Sanchez, Violeta ^a   Doxie, Deon B ^c   Opalenik, Susan R ^a   Vilgelm, Anna E ^c,d   Feld, Emily ^a   Johnson, Adam S ^a   Greenplate, Allison R ^a,c   Sanders, Melinda E ^a   Lovly, Christine M ^a,c   Frederick, Dennie T ^e   Kelley, Mark C ^a   Richmond, Ann ^c,d   Irish, Jonathan M ^a,c   Shyr, Yu ^a   Sullivan, Ryan J ^d   Puzanov, Igor ^a   Sosman, Jeffrey A ^a   Balko, Justin M ^a,c   more..

^a VANDERBILT UNIVERSITY   (United States)

^b JULES BORDET INSTITUTE   (Belgium)

^c VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d DEPARTMENT OF VETERANS AFFAIRS   (United States)

^e MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATEZOLIZUMAB; CD4 ANTIGEN; CD8 ANTIGEN; GAMMA INTERFERON; HLA DR ANTIGEN; IPILIMUMAB; LACTATE DEHYDROGENASE; MESSENGER RNA; NIVOLUMAB; PEMBROLIZUMAB; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 RECEPTOR; STAT1 PROTEIN; STAT5 PROTEIN; T LYMPHOCYTE RECEPTOR; MONOCLONAL ANTIBODY;

ANTIGEN; BIOMARKER; CANCER; GENE EXPRESSION; PHENOTYPE; PROTEIN; TUMOR;

ADULT; AGED; ALLELE; ANTIGEN EXPRESSION; ANTIGEN PRESENTATION; ANTIGEN PRESENTING CELL; ARTICLE; B LYMPHOCYTE; CANCER INFILTRATION; CANCER THERAPY; CELL FUNCTION; CELL INFILTRATION; CLINICAL ARTICLE; COHORT ANALYSIS; COMPARATIVE STUDY; CYTOTOXIC T LYMPHOCYTE; DENDRITIC CELL; FEMALE; GENE EXPRESSION; GENOTYPE; HAPLOTYPE; HELPER CELL; HUMAN; IMMUNOHISTOCHEMISTRY; LACTATE DEHYDROGENASE BLOOD LEVEL; LUNG CANCER; MAJOR HISTOCOMPATIBILITY COMPLEX; MALE; MELANOMA; MELANOMA CELL LINE; NEXT GENERATION SEQUENCING; OVERALL SURVIVAL; PHENOTYPE; PROGRESSION FREE SURVIVAL; SIGNAL TRANSDUCTION; TREATMENT RESPONSE; TUMOR CELL; ANTAGONISTS AND INHIBITORS; GENE; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; PHYSIOLOGY; TUMOR CELL LINE;

ANTIBODIES, MONOCLONAL; ANTIBODIES, MONOCLONAL, HUMANIZED; CELL LINE, TUMOR; GENE EXPRESSION REGULATION, NEOPLASTIC; GENES, MHC CLASS II; GENOTYPE; HUMANS; MELANOMA; PROGRAMMED CELL DEATH 1 RECEPTOR; RNA, MESSENGER;

EID: 84956654314     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms10582     Document Type: Article

References (48)

1. Topalian, S. L. et al. Safety, activity and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366, 2443-2454 (2012).
2. Hamid, O. et al. Safety and tumour responses with lambrolizumab (anti-PD-1) in melanoma. N. Engl. J. Med. 369, 134-144 (2013).
3. Herbst, R. S. et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515, 563-567 (2014).
4. Robert, C. et al. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med. 372, 320-330 (2014).
5. Robert, C. et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 384, 1108-1117 (2014).
6. Robert, C. et al. Pembrolizumab versus ipilimumab in advanced melanoma. N. Engl. J. Med. 372, 2521-2532 (2015).
7. Rizvi, N. A. et al. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 16, 257-265 (2015).
8. Garon, E. B. et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N. Engl. J. Med. 372, 2018-2028 (2015).
9. Gettinger, S. N. et al. Overall survival and long-term safety of nivolumab (antiprogrammed death 1 antibody, BMS-936558, ONO-4538) in patients with previously treated advanced non-small-cell lung cancer. J. Clin. Oncol. 33, 2004-2012 (2015).
10. Motzer, R. J. et al. Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J. Clin. Oncol. 33, 1430-1437 (2014).
11. Powles, T. et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 515, 558-562 (2014).
12. Ansell, S. M. et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N. Engl. J. Med. 372, 311-319 (2014).
13. Nanda, R. et al.in Proceedings of the 2014 San Antonio Breast Cancer Symposium; 9-13 December 2014; San Antonio, TX. Abstract S1-09 http://www.cancernetwork.com/sabcs-2014/immunotherapy-yields-response-triplenegative-breast-cancer#sthash.x7X0PDfh.dpuf.
14. Seiwert, T. Y. et al. A phase Ib study of MK-3475 in patients with human papillomavirus (HPV)-associated and non-HPV-associated head and neck (H/N) cancer. J. Clin. Oncol. 32, 6011 (2014).
15. Brahmer, J. R. et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumours: safety, clinical activity, pharmacodynamics, and immunologic correlates. J. Clin. Oncol. 28, 3167-3175 (2010).
16. Snyder, A. et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N. Engl. J. Med. 371, 2189-2199 (2014).
17. Yadav, M. et al. Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature 515, 572-576 (2014).
18. Tumeh, P. C. et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515, 568-571 (2014).
19. Spranger, S., Bao, R., Gajewski, T. F. Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity. Nature 523, 231-235 (2015).
20. Mellman, I., Coukos, G., Dranoff, G. Cancer immunotherapy comes of age. Nature 480, 480-489 (2011).
21. Mikucki, M. E. et al. Non-redundant requirement for CXCR3 signalling during tumoricidal T-cell trafficking across tumour vascular checkpoints. Nat. Commun. 6, 7458 (2015).
22. Garrido, F., Cabrera, T., Aptsiauri, N. "Hard" and "soft" lesions underlying the HLA class I alterations in cancer cells: implications for immunotherapy. Int. J. Cancer 127, 249-256 (2010).
23. Warabi, M., Kitagawa, M., Hirokawa, K. Loss of MHC class II expression is associated with a decrease of tumour-infiltrating T cells and an increase of metastatic potential of colorectal cancer: immunohistological and histopathological analyses as compared with normal colonic mucosa and adenomas. Pathol. Res. Pract. 196, 807-815 (2000).
24. Bernsen, M. R. et al. On the biological relevance of MHC class II and B7 expression by tumour cells in melanoma metastases. Br. J. Cancer 88, 424-431 (2003).
25. Oldford, S. A. et al. Tumour cell expression of HLA-DM associates with a Th1 profile and predicts improved survival in breast carcinoma patients. Int. Immunol. 18, 1591-1602 (2006).
26. Degenhardt, Y. et al. Distinct MHC gene expression patterns during progression of melanoma. Genes Chromosomes Cancer 49, 144-154 (2010).
27. Pollack, M. S., Heagney, S. D., Livingston, P. O., Fogh, J. HLA-A, B, C and DR alloantigen expression on forty-six cultured human tumour cell lines. J. Natl Cancer Inst. 66, 1003-1012 (1981).
28. Barbieri, G., Rimini, E., Costa, M. A. Effects of human leukocyte antigen (HLA)-DR engagement on melanoma cells. Int. J. Oncol. 38, 1589-1595 (2011).
29. Colloby, P. S., West, K. P., Fletcher, A. Is poor prognosis really related to HLA-DR expression by malignant melanoma cells? Histopathology 20, 411-416 (1992).
30. Chornoguz, O., Gapeev, A., O'Neill, M. C., Ostrand-Rosenberg, S. Major histocompatibility complex class II\+ invariant chain negative breast cancer cells present unique peptides that activate tumour-specific T cells from breast cancer patients. Mol. Cell Proteomics 11, 1457-1467 (2012).
31. Londei, M., Lamb, J. R., Bottazzo, G. F., Feldmann, M. Epithelial cells expressing aberrant MHC class II determinants can present antigen to cloned human T cells. Nature 312, 639-641 (1984).
32. Meazza, R., Comes, A., Orengo, A. M., Ferrini, S., Accolla, R. S. Tumour rejection by gene transfer of the MHC class II transactivator in murine mammary adenocarcinoma cells. Eur. J. Immunol. 33, 1183-1192 (2003).
33. Rizvi, N. A. et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348, 124-128 (2015).
34. Wellbrock, C. et al. STAT5 contributes to interferon resistance of melanoma cells. Curr. Biol. 15, 1629-1639 (2005).
35. Lee, Y. S., Kim, S. H., Cho, J. A., Kim, C. W. Introduction of the CIITA gene into tumour cells produces exosomes with enhanced anti-tumour effects. Exp. Mol. Med. 43, 281-290 (2011).
36. Joseph, R. W. et al. Correlation of NRAS mutations with clinical response to high-dose IL-2 in patients with advanced melanoma. J. Immunother. 35, 66-72 (2012).
37. Johnson, D. B. et al. Impact of NRAS mutations for patients with advanced melanoma treated with immune therapies. Cancer Immunol. Res. 3, 288-295 (2015).
38. Loor, F., Kindred, B. Differentiation of T-cell precursors in nude mice demonstrated by immunofluorescence of T-cell membrane markers. J. Exp. Med. 138, 1044-1055 (1973).
39. Rodriguez, T. et al. Patterns of constitutive and IFN-gamma inducible expression of HLA class II molecules in human melanoma cell lines. Immunogenetics 59, 123-133 (2007).
40. Wolchok, J. D. et al. Nivolumab plus ipilimumab in advanced melanoma. N. Engl. J. Med. 369, 122-133 (2013).
41. Postow, M. A. et al. Nivolumab and Ipilimumab versus ipilimumab in untreated melanoma. N. Engl. J. Med. 372, 2006-2017 (2015).
42. Larkin, J. et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N. Engl. J. Med. 373, 23-34 (2015).
43. Balko, J. M. et al. Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance. Nat. Med. 18, 1052-1059 (2012).
44. Balko, J. M. et al. Activation of MAPK pathways due to DUSP4 loss promotes cancer stem cell-like phenotypes in basal-like breast cancer. Cancer Res. 73, 6346-6358 (2013).
45. R Development Core Team. R: A language and environment for statistical computing (R Foundation for Statistical Computing, Vienna, Austria, 2015).
46. Benjamini, Y., Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Series B Stat. Methodol. 57, 289-300 (1995).
47. Efron, B., Tibshirani, R. On testing the significance of sets of genes. Ann. Appl. Stat. 1, 107-129 (2007).
48. Barretina, J. et al. The cancer cell line encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483, 603-607 (2012).