Colorectal cancer (CRC) is the most prevalent malignancie worldwide and stands as the 2nd leading cause of cancer-related mortality and the 3rd most frequently diagnosed cancer, showing its substantial impact on global health. While advances in screening and treatment have improved, the clinical management of CRC, mainly in advanced stages pose substantial encounters. Immunotherapy, especially immune checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4 pathways, has emerged as a promising therapeutic strategy. Agents such as ipilimumab, nivolumab and pembrolizumab have demonstrated clinical benefits in select CRC populations, notably those with mismatch repair deficiency or high microsatellite instability. However, the broader application of ICIs is often constrained by immune-related adverse events (IRAEs), including colitis and severe diarrhea, which compromises treatment adherence and patient quality of life. Increasing attention has turned to natural bioactive compounds (curcumin and resveratrol)-for their immunomodulatory and anti-inflammatory properties. Preclinical and early clinical evidence suggests these compounds may not only enhances the efficacy of ICIs but also reduces the IRAEs. This review explores current immunotherapeutic strategies in CRC, evaluates the role of natural immunomodulators as adjuncts to ICIs, and discusses emerging tools such as the immunoscore (IS) for predicting treatment response. By integrating novel combination approaches and predictive biomarkers, future strategies may improve both the effectiveness and safety of immunotherapy in CRC management.
Sharma et al. (Wed,) studied this question.
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