Intratumoral amino acid insufficiency limits CD8⁺ T-cell effector function.

ABSTRACT: Loss of effector function is a hallmark of tumor-infiltrating CD8⁺ T-cells that have lost therapeutic efficacy. This impaired capacity occurs despite expression of transcripts encoding cytotoxic proteins, raising the possibility that post-transcriptional suppression of cytotoxic protein synthesis limits anti-tumor immunity. Whether altered protein synthesis contributes to CD8⁺ T-cell dysfunction has not been explored. Here we show that intratumoral amino acid availability restricts the cytotoxic capacity of CD8⁺ TILs by perturbing their ability to sustain protein synthesis. mRNA translation rates in antigen-specific CD8⁺ T-cells were rapidly and specifically suppressed within tumors but not tumor-draining lymph nodes, due to a combination of incr

SUBMITTER: Chen YT 

PROVIDER: S-EPMC12248039 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature