A novel analysis published in Oncotarget highlights the immunomodulatory role of CHEK2 gene deficiency in solid tumors, extending beyond its classical DNA repair functions. Loss of CHEK2 impairs homologous recombination, elevating tumor mutational burden and neoantigen presentation, thereby potentially increasing responsiveness to immune checkpoint inhibitors. Additionally, CHEK2 deficiency activates the cGAS-STING pathway, inducing a pro-inflammatory microenvironment conducive to T cell infiltration. These mechanistic insights reveal CHEK2 as a promising biomarker to optimize patient selection for immunotherapy and pave the way for targeted therapeutic strategies enhancing antitumor immunity.