| First Author | Ma X | Year | 2021 |
| Journal | Cell Metab | Volume | 33 |
| Issue | 5 | Pages | 1001-1012.e5 |
| PubMed ID | 33691090 | Mgi Jnum | J:305972 |
| Mgi Id | MGI:6707887 | Doi | 10.1016/j.cmet.2021.02.015 |
| Citation | Ma X, et al. (2021) CD36-mediated ferroptosis dampens intratumoral CD8(+) T cell effector function and impairs their antitumor ability. Cell Metab 33(5):1001-1012.e5 |
| abstractText | 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. |
