The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies

Shogo Kumagai, Yosuke Togashi, Takahiro Kamada, Eri Sugiyama, Hitomi Nishinakamura, Yoshiko Takeuchi, Kochin Vitaly, Kota Itahashi, Yuka Maeda, Shigeyuki Matsui, Takuma Shibahara, Yasuho Yamashita, Takuma Irie, Ayaka Tsuge, Shota Fukuoka, Akihito Kawazoe, Hibiki Udagawa, Keisuke Kirita, Keiju Aokage, Genichiro IshiiTakeshi Kuwata, Kenta Nakama, Masahito Kawazu, Toshihide Ueno, Naoya Yamazaki, Koichi Goto, Masahiro Tsuboi, Hiroyuki Mano, Toshihiko Doi, Kohei Shitara, Hiroyoshi Nishikawa

Research output: Contribution to journalArticlepeer-review

138 Citations (Scopus)

Abstract

Immune checkpoint blockade has provided a paradigm shift in cancer therapy, but the success of this approach is very variable; therefore, biomarkers predictive of clinical efficacy are urgently required. Here, we show that the frequency of PD-1+CD8+ T cells relative to that of PD-1+ regulatory T (Treg) cells in the tumor microenvironment can predict the clinical efficacy of programmed cell death protein 1 (PD-1) blockade therapies and is superior to other predictors, including PD ligand 1 (PD-L1) expression or tumor mutational burden. PD-1 expression by CD8+ T cells and Treg cells negatively impacts effector and immunosuppressive functions, respectively. PD-1 blockade induces both recovery of dysfunctional PD-1+CD8+ T cells and enhanced PD-1+ Treg cell–mediated immunosuppression. A profound reactivation of effector PD-1+CD8+ T cells rather than PD-1+ Treg cells by PD-1 blockade is necessary for tumor regression. These findings provide a promising predictive biomarker for PD-1 blockade therapies.

Original languageEnglish
Pages (from-to)1346-1358
Number of pages13
JournalNature Immunology
Volume21
Issue number11
DOIs
Publication statusPublished - Nov 1 2020
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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