New strategies to enhance the efficacy of PD-1/PD-L1 inhibitors in treating microsatellite stable colorectal cancer.

Immune checkpoint therapy has demonstrated significant potential in the treatment of various solid tumors. Among these, tumor-induced immunosuppression mediated by programmed cell death protein 1 (PD-1) represents a critical checkpoint. PD-1/programmed death-ligand 1 (PD-L1) inhibitors have been proven to exhibit substantial efficacy in solid tumors such as melanoma and bladder cancer. In colorectal cancer (CRC) treatment, their therapeutic effect is more pronounced in "hot" tumors compared to "cold" tumors with proficient mismatch repair (pMMR) and microsatellite stable (MSS) characteristics. However, only approximately 15% of CRC patients exhibit microsatellite instability-high (MSI-H) features. Consequently, to facilitate the conversion of "cold" tumors into "hot" tumors, this study found that combination treatment plans involving PD-1/PD-L1 inhibitors alongside chemotherapy, radiotherapy, targeted therapy, and anti-angiogenic drugs yield superior outcomes compared to monotherapy. This review focuses on recent research advancements in enhancing the immunotherapeutic efficacy of PD-1/PD-L1 inhibitors in MSS CRC, while systematically elucidating the mechanisms of immune resistance in MSS-type "cold" tumors and their potential therapeutic targets.