Tissue specificity and chromosomal alterations shape divergent immune programs in HRD tumors.

ABSTRACT: Homologous recombination deficiency (HRD) activates pro-inflammatory cGAS/STING signaling, positioning it as a biomarker for combining immune checkpoint blockade (ICB) and PARP inhibition (PARPi). However, the consequences of HRD on the immune landscape across cancers remain unclear. Here, we applied a pan-cancer HRD classifier to >10,000 tumors from The Cancer Genome Atlas and uncovered striking heterogeneity in immune activity. Compared to HR-proficient tumors, HRD tumors showed elevated inflammation in breast, ovarian, and endometrial cancers. These tumors exhibited robust activation of innate and adaptive immune pathways (IFN, NF-κB) and transcriptional hallmarks of senescence, angiogenesis, and adenosine signaling. In contrast, lung, head and neck, and melanoma HRD tumors displayed su

SUBMITTER: Gulhan DC 

PROVIDER: S-EPMC12633024 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature