Allele-specific HLA LOH in solid tumors: distinct patterns by tumor type and potential prognostic relevance.

ABSTRACT: T-cell receptors (TCRs) recognize antigens derived from fragments of somatically expressed proteins that are degraded by the proteasome and presented by specific human leukocyte antigen (HLA) molecules. Recent therapeutic advances using the TCR as a tumor-targeting moiety have focused attention on HLA loss of heterozygosity (LOH) as a potential resistance mechanism. Allele-specific LOH, rather than allele-agnostic, is particularly pertinent, but rarely evaluated. Using a real-world dataset comprising 78,418 cases, we demonstrate that allele-specific LOH occurs at a relatively low frequency (<10%) across all patients with cancer. We observed a modest increase in allele-specific HLA LOH in cancers harboring associated neoantigen driver mutations (eg, KRAS or TP53

SUBMITTER: Sewastianik T 

PROVIDER: S-EPMC12421593 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature