| Literature DB >> 26359337 |
Eliezer M Van Allen1,2,3, Diana Miao1,2, Bastian Schilling4,5, Sachet A Shukla1,2, Christian Blank6, Lisa Zimmer4,5, Antje Sucker4,5, Uwe Hillen4,5, Marnix H Geukes Foppen6, Simone M Goldinger7, Jochen Utikal5,8,9, Jessica C Hassel10, Benjamin Weide11, Katharina C Kaehler12, Carmen Loquai13, Peter Mohr14, Ralf Gutzmer15, Reinhard Dummer7, Stacey Gabriel2, Catherine J Wu1,2, Dirk Schadendorf4,5, Levi A Garraway1,2,3.
Abstract
Monoclonal antibodies directed against cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), such as ipilimumab, yield considerable clinical benefit for patients with metastatic melanoma by inhibiting immune checkpoint activity, but clinical predictors of response to these therapies remain incompletely characterized. To investigate the roles of tumor-specific neoantigens and alterations in the tumor microenvironment in the response to ipilimumab, we analyzed whole exomes from pretreatment melanoma tumor biopsies and matching germline tissue samples from 110 patients. For 40 of these patients, we also obtained and analyzed transcriptome data from the pretreatment tumor samples. Overall mutational load, neoantigen load, and expression of cytolytic markers in the immune microenvironment were significantly associated with clinical benefit. However, no recurrent neoantigen peptide sequences predicted responder patient populations. Thus, detailed integrated molecular characterization of large patient cohorts may be needed to identify robust determinants of response and resistance to immune checkpoint inhibitors.Entities:
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Year: 2015 PMID： 26359337 PMCID： PMC5054517 DOI： 10.1126/science.aad0095
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728