Distinct immune cell populations define response to anti-PD-1 monotherapy and anti-PD-1/anti-CTLA-4 combined therapy

Tuba N. Gide, Camelia Quek, Alexander M. Menzies, Annie T. Tasker, Ping Shang, Jeff Holst, Jason Madore, Su Yin Lim, Rebecca Velickovic, Matthew Wongchenko, Yibing Yan, Serigne Lo, Matteo S. Carlino, Alexander Guminski, Robyn P. M. Saw, Angel Pang, Helen M. McGuire, Umaimainthan Palendira, John F. Thompson, Helen Rizos & 5 others Ines Pires da Silva, Marcel Batten, Richard A. Scolyer, Georgina V. Long, James S. Wilmott*

*Corresponding author for this work

Research output: Contribution to journalArticle

74 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)238-255.e6
Number of pages24
JournalCancer Cell
Volume35
Issue number2
DOIs
Publication statusPublished - 11 Feb 2019

Keywords

  • anti-CTLA-4
  • anti-PD-1
  • combination therapy
  • EOMES
  • immune checkpoint inhibitors
  • immunotherapy
  • melanoma
  • predictive biomarkers
  • resistance mechanisms
  • RNA-seq

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