Journal
CANCER CELL
Volume 35, Issue 2, Pages 238-+Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2019.01.003
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Funding
- Melanoma Institute Australia
- New South Wales Department of Health
- NSW Health Pathology
- National Health and Medical Research Council of Australia (NHMRC) [APP1093017]
- Cancer Institute NSW
- NHMRC Fellowships
- University of Sydney Medical Foundation
- University of Sydney
- Cancer Institute NSW Fellowship
- Melanoma Foundation of the University of Sydney
- Cancer Council NSW [RG18-08, RG17-04]
- Australian Cancer Research Foundation (Tumor Metabolism Laboratory)
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Cancer immunotherapies provide survival benefits in responding patients, but many patients fail to respond. Identifying the biology of treatment response and resistance are a priority to optimize drug selection and improve patient outcomes. We performed transcriptomic and immune profiling on 158 tumor biopsies from melanoma patients treated with anti-PD-1 monotherapy (n = 63) or combined anti-PD-1 and anti-CTLA-4 (n = 57). These data identified activated T cell signatures and T cell populations in responders to both treatments. Further mass cytometry analysis identified an EOMES(+)CD69(+)CD45RO(+) effector memory T cell phenotype that was significantly more abundant in responders to combined immunotherapy compared with non-responders (n = 18). The gene expression profile of this population was associated with longer progression-free survival in patients treated with single agent and greater tumor shrinkage in both treatments.
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