In Genecast Cohort, seventy of 406 (17.2%) patients were identified genomic alterations in HRR-gene, the most frequently mutated genes were ATM (9%), BRCA2 (4%), ATR (3%), RAD50 (3%) and BRIP1 (3%). In MSK-COAD cohort (treated with immune checkpoint inhibitors), HRR-mut group (n = 34) had a significantly better OS than HRR-wt group (n = 50) (log-rank test, P = 0.0087)....Mutations of HRR-gene could significantly increase immune activity in patients with MSS COAD, implying the feasibility of using HRR-mut as a response predictor of immunotherapy in MSS-COAD.