The DNA damage response and cancer immunotherapy

A comprehensive review in Nature Reviews Cancer synthesizes how defects in DNA damage response (DDR) pathways enhance tumour immunogenicity and modulate sensitivity to immune checkpoint inhibitors across cancer types. The authors identify shared immunological consequences — including elevated tumour mutational burden and activation of the cGAS-STING pathway — that arise from distinct DDR alterations such as BRCA1/2, ATM, and mismatch repair deficiency. They evaluate emerging combination strategies pairing DDR-targeting agents (PARP inhibitors, ATR/CHK1 inhibitors) with immunotherapy, and delineate mechanisms of primary and acquired resistance relevant to clinical trial design.