MTOR-dependent translation drives tumor infiltrating CD8⁺ effector and CD4⁺ Treg cells expansion.

ABSTRACT: We performed a systematic analysis of the translation rate of tumor-infiltrating lymphocytes (TILs) and the microenvironment inputs affecting it, both in humans and in mice. Measurement of puromycin incorporation, a proxy of protein synthesis, revealed an increase of translating CD4⁺ and CD8⁺ cells in tumors, compared to normal tissues. High translation levels are associated with phospho-S6 labeling downstream of mTORC1 activation, whereas low levels correlate with hypoxic areas, in agreement with data showing that T cell receptor stimulation and hypoxia act as translation stimulators and inhibitors, respectively. Additional analyses revealed the specific phenotype of translating TILs. CD8⁺ translating cells have enriched expression of IFN-γ and CD-39, and

SUBMITTER: De Ponte Conti B 

PROVIDER: S-EPMC8598161 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature