TMED inhibition suppresses cell surface PD-1 expression and overcomes T cell dysfunction.

ABSTRACT:

Background

Blockade of the programmed cell death protein 1 (PD-1) immune checkpoint (ICB) is revolutionizing cancer therapy, but little is known about the mechanisms governing its expression on CD8 T cells. Because PD-1 is induced during activation of T cells, we set out to uncover regulators whose inhibition suppresses PD-1 abundance without adversely impacting on T cell activation.

Methods

To identify PD-1 regulators in an unbiased fashion, we performed a whole-genome, fluorescence-activated cell sorting (FACS)-based CRISPR-Cas9 screen in primary murine CD8 T cells. A dual-readout design using the activation marker CD137 allowed us to uncouple genes involved in PD-1 regulation from those governing general T cell activation.

Results

We found that the inactivation of

SUBMITTER: Vredevoogd DW 

PROVIDER: S-EPMC11552591 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature