articleAdvanced ScienceJan 12, 2026GOLD OA

T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities

YYYu YangXYXiaoyu YaoQWQingyang WangMYMengrui YangRLRui Li

Macau University of Science and Technology · University of Macau · +5 more institutions

PubMed
Indexed incrossrefdoajpubmed

Abstract

ABSTRACT T cell exhaustion represents a pivotal mechanism of immune escape in cancer, with its inherent heterogeneity and dynamic plasticity being key determinants of the variable responses and resistance to immune checkpoint inhibitors (ICIs). This review comprehensively delineates the multifaceted heterogeneity of exhausted T (T EX ) cells, tracing their developmental trajectory from precursor exhausted T (T PEX ) cells to terminally differentiated exhausted T (T EX ‐term ) cells. We highlight both distinct and shared exhaustion features across diverse cancer types and spatial niches within the tumor microenvironment. Furthermore, we examine the multi‐layer biomarkers that drive and define this state,…

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7
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84.90
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100%
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357
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8

Topics & keywords

Topics
Keywords
  • T cell
  • Chimeric antigen receptor
  • Immune system
  • Immunotherapy
  • Cancer
  • Tumor microenvironment
  • Cell
  • Epigenetics
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