Cystine deprivation triggers CD36-mediated ferroptosis and dysfunction of tumor infiltrating CD8⁺ T cells.

ABSTRACT: Cancer cells develop multiple strategies to evade T cell-mediated killing. On one hand, cancer cells may preferentially rely on certain amino acids for rapid growth and metastasis. On the other hand, sufficient nutrient availability and uptake are necessary for mounting an effective T cell anti-tumor response in the tumor microenvironment (TME). Here we demonstrate that tumor cells outcompete T cells for cystine uptake due to high Slc7a11 expression. This competition induces T-cell exhaustion and ferroptosis, characterized by diminished memory formation and cytokine secretion, increased PD-1 and TIM-3 expression, as well as intracellular oxidative stress and lipid-peroxide accumulation. Importantly, either Slc7a11 deletion in tumor cells or intratumoral cystine supplementation improves T c

SUBMITTER: Han C 

PROVIDER: S-EPMC10869360 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature