This combination therapy significantly enhanced antitumor efficacy and promoted long‐term tumor‐specific immune memory in microsatellite stable colorectal cancer liver metastasis (MSS‐CRLM) models by increasing neoantigen‐specific Rgs2+CD8+ T cells infiltration and reprogramming the immunosuppressive tumor microenvironment (TME), providing novel immunotherapy insights for MSS‐CRLM patients. This evidence concerns the gene RGS2 and neoplasm.