High TMB can enhance the effectiveness of ICIs by increasing the number of targets (neoantigens) available for immune recognition. A subset of CRCs exhibit high microsatellite instability, which often correlates with high TMB. High microsatellite instability CRCs are more responsive to ICIs. Colorectal cancers with mismatch repair deficiency (dMMR), leading to high microsatellite instability (MSI-H), tends to have a high TMB. These tumors are more likely to respond to ICIs such as pembrolizumab and nivolumab. TMB is an important biomarker in the immuno-oncology landscape for colorectal cancer. It helps identify patients who are more likely to respond to ICIs, particularly in the context of high microsatellite instability or mismatch repair deficiency tumors. Ongoing research is focused on refining the use of TMB, exploring its potential in combination therapies, and integrating it with other biomarkers to enhance the efficacy of immunotherapy in colorectal cancer. • TMB | Head and neck squamous cell carcinoma (HNSCC)