Synergistic immunomodulation: integrating physical ablation with immune checkpoint inhibitors for metastatic colorectal carcinoma

Colorectal carcinoma (CRC) is one of the most common malignant tumors worldwide, with treatment options including surgery, chemotherapy, radiotherapy, and targeted therapy. However, the overall efficacy of treatment for metastatic CRC (mCRC) remains unsatisfactory. In recent years, immune checkpoint inhibitors (ICIs) have shown good therapeutic effects in some patients, but the overall response rate remains low. Physical ablation (PA) is a localized treatment modality that, in addition to eradicating targeted lesions, promotes anti-tumor immunity by releasing tumor-associated antigens from damaged tumor cells. ICIs enhance this PA-elicited anti-tumor immune response by inhibiting immunosuppressive pathways and unleashing T-cell activity, resulting in a synergistic anti-tumor effect. This article reviews the latest research on the treatment of mCRC with PA (mainly including radiofrequency ablation, microwave ablation, and cryoablation) combined with ICIs, focusing on how PA combined with ICIs can reshape the tumor immune microenvironment to produce a synergistic anti-tumor immune response. Finally, this article also discusses the challenges currently faced by the combined treatment and looks forward to future research directions, aiming to provide a new treatment strategy to improve the clinical prognosis of mCRC.