Robin Park, MD

Why do T-cell therapies work in blood cancers but struggle in solid tumors? A @Nature study from @jccarnevale’s lab, led by Qi Liu (@GladstoneInst @UCSF), ran genome-wide CRISPR screens on human T cells inside tumors, not in a dish. Two especially interesting hits emerged, each blocking a different step: P2RY8 keeps T cells from getting into the tumor. GNAS is where many of the tumor’s “stand down” signals converge. Delete GNAS, and T cells become resistant to several of those suppressive cues at once. Delete both: in one preclinical model, 4 of 6 mice cleared their tumors, vs 1 of 6 with GNAS deletion alone. A clever demonstration that the tumor itself can help reveal what to engineer into better T-cell therapies.