Disruption of CISH promotes the antitumor activity of human T cells and decreases PD-1 expression levels

CISH, a member of the SOCS family, inhibits JAK-STAT and TCR signaling in T and NK cells. However, its role in the regulation of immune checkpoints in T cells remains unclear.

In this study, we ablated CISH in T cells with CRISPR/Cas9 and found that the sensitivity of T cells to TCR and cytokine stimulation was increased. In addition, chimeric antigen receptor T cells with CISH deficiency exhibited longer survival and higher cytokine secretion and antitumor activity. Notably, PD-1 expression was decreased in activated CISH-deficient T cells in vitro and in vivo.