TY - JOUR TI - mTOR-dependent translation drives tumor infiltrating CD8+ effector and CD4+ Treg cells expansion AU - De Ponte Conti, Benedetta AU - Miluzio, Annarita AU - Grassi, Fabio AU - Abrignani, Sergio AU - Biffo, Stefano AU - Ricciardi, Sara A2 - Topisirovic, Ivan A2 - Rothlin, Carla V A2 - Topisirovic, Ivan A2 - Larsson, Ola VL - 10 PY - 2021 DA - 2021/11/17 SP - e69015 C1 - eLife 2021;10:e69015 DO - 10.7554/eLife.69015 UR - https://doi.org/10.7554/eLife.69015 AB - 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 reduced SLAMF6, pointing to a cytotoxic phenotype. CD4+ translating cells are mostly regulatory T cells (Tregs) with enriched levels of CTLA-4 and Ki67, suggesting an expanding immunosuppressive phenotype. In conclusion, the majority of translationally active TILs is represented by cytotoxic CD8+ and suppressive CD4+ Tregs, implying that other subsets may be largely composed by inactive bystanders. KW - CD4+ KW - CD8+ KW - Treg KW - translation JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -