Title of article - MEDICINE. Membrane traffic en route to cancer.
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.
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Department of Cell Biology and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University, New Haven, CT 06510, USA.
Details of Journal for MEDICINE. Membrane traffic en route to cancer.
Journal Title - Science (New York, N.Y.)
ISSN - 1095-9203
Volume - 350
Issue - 6257
Publish date - 2015-Oct
Language - eng
Country - United States
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