CD36-mediated ferroptosis dampens intratumoral CD8+ T cell effector function and impairs their antitumor ability

Xingzhe Ma, Liuling Xiao, Lintao Liu, Lingqun Ye, Pan Su, Enguang Bi, Qiang Wang, Maojie Yang, Jianfei Qian, Qing Yi

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Understanding the mechanisms underlying how T cells become dysfunctional in a tumor microenvironment (TME) will greatly benefit cancer immunotherapy. We found that increased CD36 expression in tumor-infiltrating CD8+ T cells, which was induced by TME cholesterol, was associated with tumor progression and poor survival in human and murine cancers. Genetic ablation of Cd36 in effector CD8+ T cells exhibited increased cytotoxic cytokine production and enhanced tumor eradication. CD36 mediated uptake of fatty acids by tumor-infiltrating CD8+ T cells in TME, induced lipid peroxidation and ferroptosis, and led to reduced cytotoxic cytokine production and impaired antitumor ability. Blocking CD36 or inhibiting ferroptosis in CD8+ T cells effectively restored their antitumor activity and, more importantly, possessed greater antitumor efficacy in combination with anti-PD-1 antibodies. This study reveals a new mechanism of CD36 regulating the function of CD8+ effector T cells and therapeutic potential of targeting CD36 or inhibiting ferroptosis to restore T cell function.

Original languageEnglish (US)
Pages (from-to)1001-1012.e5
JournalCell Metabolism
Issue number5
StatePublished - May 4 2021


  • CD36
  • CD8 T cells
  • ferroptosis
  • lipid peroxidation

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology


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