Mechanisms of resistance to immune checkpoint inhibitors

Research output: Contribution to journalReview articlepeer-review

25 Citations (Scopus)

Abstract

Immune checkpoint inhibitors (ICIs) are effective for various types of cancer, and their application has led to paradigm shifts in cancer treatment. While many patients can obtain clinical benefits from ICI treatment, a large number of patients are primarily resistant to such treatment or acquire resistance after an initial response. Thus, elucidating the resistance mechanisms is warranted to improve the clinical outcomes of ICI treatment. ICIs exert their antitumor effects by activating T cells in the tumor microenvironment. There are various resistance mechanisms, such as insufficient antigen recognition by T cells, impaired T-cell migration and/or infiltration, and reduced T-cell cytotoxicity, most of which are related to the T-cell activation process. Thus, we classify them into three main mechanisms: resistance mechanisms related to antigen recognition, T-cell migration and/or infiltration, and effector functions of T cells. In this review, we summarize these mechanisms of resistance to ICIs related to the T-cell activation process and progress in the development of novel therapies that can overcome resistance.

Original languageEnglish
Pages (from-to)3303-3312
Number of pages10
JournalCancer Science
Volume113
Issue number10
DOIs
Publication statusPublished - Oct 2022

Keywords

  • T cell
  • cancer immunology
  • exhaustion
  • immune checkpoint inhibitor
  • resistance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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