Massively parallel interrogation of human functional variants modulating cancer immunosurveillance.

ABSTRACT: Anti-PD-1/PD-L1 immune checkpoint blockade (ICB) therapy has revolutionized clinical cancer treatment, while abnormal PD-L1 or HLA-I expression in patients can significantly impact the therapeutic efficacy. Somatic mutations in cancer cells that modulate these critical regulators are closely associated with tumor progression and ICB response. However, a systematic interpretation of cancer immune-related mutations is still lacking. Here, we harnessed the ABEmax system to establish a large-scale sgRNA library encompassing approximately 820,000 sgRNAs that target all feasible serine/threonine/tyrosine residues across the human genome, which systematically unveiled thousands of novel mutations that decrease or augment PD-L1 or HLA-I expression. Beyond residues associated with phosphorylation e

SUBMITTER: Liu Y 

PROVIDER: S-EPMC11920242 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature