In recent years, immunotherapy has gained prominence both as a therapeutic option and as a major topic of cancer research. Despite this progress, the effectiveness of immune checkpoint inhibitors (ICI) in colorectal cancer remains limited, largely because current biomarkers can identify only a small fraction of patients who will benefit. Since chemokine signaling plays a key role in guiding immune cell recruitment and shaping antitumor immunity, this study examined whether alterations in chemokine-related genes influence outcomes in colon adenocarcinoma (COAD) patients treated with ICIs.Clinical and genomic data from an ICI-treated COAD cohort were obtained from cBioPortal and integrated with datasets from The Cancer Genome Atlas (TCGA). These resources were used to characterize mutation patterns, immunogenic features, and tumor microenvironment (TME) differences associated with distinct chemokine mutation profiles. Cox regression analyses indicated that patients with a high chemokine-mutation burden experienced significantly better survival following ICI therapy. According to CIBERSORT results, this subgroup displayed greater infiltration of M1 macrophages, neutrophils, and activated natural killer (NK) cells. Measures of immunogenicity—including tumor mutation burden (TMB), neoantigen load (NAL), DNA damage repair (DDR) pathway mutations, and microsatellite instability–high (MSI-H)—were also elevated in the high-mutation group. Overall, our findings suggest that the mutational status of the chemokine signaling pathway is strongly associated with ICI treatment outcomes in COAD. Enhanced genomic instability and a more immune-active TME may underlie the improved prognosis observed in patients with a high chemokine-mutation load, offering a potential direction for refining immunotherapy selection in COAD.
