PT  - JOURNAL ARTICLE
AU  - Aurélien Sutra Del Galy
AU  - Silvia Menegatti
AU  - Jaime Fuentealba
AU  - Laetitia Perrin
AU  - Francesca Lucibello
AU  - Julie Helft
AU  - Aurélie Darbois
AU  - Michael Saitakis
AU  - Jimena Tosello
AU  - Derek Rookhuizen
AU  - Marc Deloger
AU  - Pierre Gestraud
AU  - Gérard Socié
AU  - Sebastian Amigorena
AU  - Olivier Lantz
AU  - Laurie Menger
TI  - In vivo genome-wide CRISPR screens identify SOCS1 as a major intrinsic checkpoint of CD4<sup>+</sup> Th1 cell response
AID  - 10.1101/2021.04.12.439455
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.12.439455
4099  - http://biorxiv.org/content/early/2021/04/12/2021.04.12.439455.short
4100  - http://biorxiv.org/content/early/2021/04/12/2021.04.12.439455.full
AB  - The expansion of antigen experienced CD4+ T cells is limited by intrinsic factors. Using in vivo genome-wide CRISPR-Cas9 screens, we identified SOCS1 as a non-redundant checkpoint imposing a brake on CD4+ T-cell proliferation upon rechallenge. We show here that SOCS1 is a critical node integrating both IL-2 and IFN-γ signals and blocking multiple signaling pathways to abrogate CD4+ Th1 cell response. In CD8+ T-cell, SOCS1 does not impact the proliferation but rather reduces survival and effector functions. By targeting SOCS1, both murine and human CD4+ T-cell antitumor adoptive therapies exhibit a restored intra-tumor accumulation, proliferation/survival, persistence and polyfunctionality, promoting long term rejection of established tumors. These findings identify SOCS1 as a major intracellular checkpoint inhibitor of primed CD4+ T cells, opening new possibilities to optimize CAR-T cell therapies composition and efficacy.Competing Interest StatementThe authors have declared no competing interest.