Surfaceome CRISPR activation screening uncovers ligands regulating tumor sensitivity to NK cell killing.

Surfaceome CRISPRa screening identifies key tumor surface ligands, including CD43, that regulate susceptibility to NK cell killing, revealing new therapeutic targets.

• Why it matters: Understanding molecular factors that influence tumor sensitivity to NK cytotoxicity is crucial for improving immunotherapy strategies, yet these determinants are not fully known.
• What they did: Using a surfaceome-focused CRISPRa library, the study screened human and murine cancer cells co-cultured with NK cells, uncovering both known and novel regulators like CD44, PDPN, and Siglec-1/CD169.
• The result: Disruption of these ligands altered NK cell killing in vitro and in humanized mice, and targeting CD43 on NK or CAR T cells significantly boosted leukemia cell cytotoxicity, advancing immunotherapy approaches.