| Literature DB >> 30753825 |
Tuba N Gide1, Camelia Quek1, Alexander M Menzies2, Annie T Tasker3, Ping Shang3, Jeff Holst4, Jason Madore3, Su Yin Lim5, Rebecca Velickovic3, Matthew Wongchenko6, Yibing Yan6, Serigne Lo3, Matteo S Carlino7, Alexander Guminski2, Robyn P M Saw8, Angel Pang4, Helen M McGuire9, Umaimainthan Palendira4, John F Thompson8, Helen Rizos5, Ines Pires da Silva1, Marcel Batten1, Richard A Scolyer8, Georgina V Long2, James S Wilmott10.
Abstract
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.Entities:
Keywords: EOMES; RNA-seq; anti-CTLA-4; anti-PD-1; combination therapy; immune checkpoint inhibitors; immunotherapy; melanoma; predictive biomarkers; resistance mechanisms
Year: 2019 PMID： 30753825 DOI： 10.1016/j.ccell.2019.01.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743