Current Strategies and Emerging Paradigms of Immunotherapy in Microsatellite Stable Colorectal Cancer: A Review...

Immunotherapy, especially through the innovative use of immune checkpoint inhibitors (ICIs), has rapidly become an essential component in both first-line and subsequent treatment strategies for cancers that exhibit DNA mismatch repair defects or display high microsatellite instability (dMMR/MSI-H). These therapies harness the power of the immune system to target and destroy cancer cells more effectively. However, the application of ICIs in patients diagnosed with microsatellite stable (MSS) colorectal cancer presents considerable hurdles. These challenges largely arise from the inherent tumor heterogeneity and the complex immune landscape characteristic of the tumor microenvironment. It is crucial to highlight that numerous clinical trials are actively underway, aimed at deepening our understanding of the mechanisms at play and paving the way for future advancements in this arena. This article endeavors to provide an extensive review of the current literature surrounding the application of ICIs in MSS colorectal cancer. We aim to deliver a thorough overview of the present state of immunotherapy for this subset of colorectal cancer, beginning with an exploration of various combination therapy strategies that enhance immune responses. Moreover, we will investigate several adverse prognostic factors that affect MSS colorectal cancer patients undergoing immunotherapy. A particular focus will be placed on the detrimental effects of liver metastasis and the influence of local treatment modalities for liver metastasis on patient clinical outcomes. This narrative review compiles current knowledge to serve as a reference point for identifying potential patient populations that could benefit from immunotherapy in the future, ultimately striving for improved therapeutic approaches and patient outcomes.