Internal checkpoint regulates T cell neoantigen reactivity and susceptibility to PD1 blockade.

ABSTRACT:

Background

Adoptive transfer of tumor-infiltrating lymphocytes (TIL) fails to consistently elicit tumor rejection. Manipulation of intrinsic factors that inhibit T cell effector function and neoantigen recognition may therefore improve TIL therapy outcomes. We previously identified the cytokine-induced SH2 protein (CISH) as a key regulator of T cell functional avidity in mice. Here, we investigate the mechanistic role of CISH in regulating human T cell effector function in solid tumors and demonstrate that CRISPR/Cas9 disruption of CISH enhances TIL neoantigen recognition and response to checkpoint blockade.

Methods

Single-cell gene expression profiling was used to identify a negative correlation between high CISH expression and TIL activation in patient-derived TIL. A GMP-c

SUBMITTER: Palmer DC 

PROVIDER: S-EPMC9847506 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature