Epigenetic regulation of cell state by H2AFY governs immunogenicity in high-risk neuroblastoma.

Childhood neuroblastoma with MYCN amplification is classified as high risk and often relapses after intensive treatments. Immune checkpoint blockade therapy against the PD-1/L1 axis shows limited efficacy in patients with neuroblastoma, and the cancer intrinsic immune regulatory network is poorly understood. Here, we leverage genome-wide CRISPR/Cas9 screens and identify H2AFY as a resistance gene to the clinically approved PD-1 blocking antibody nivolumab.