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Immunotherapy is becoming as a major treatment modality for multiple types of solid tumors, including subsets of colorectal cancers (CRCs). The successes with immunotherapy alone has largely been achieved in patients with advanced-stage mismatch-repair-deficient and microsatellite instability-high (dMMR–MSI-H) CRCs. However, the benefits of immunotherapy have not been demonstrated to be effective in patients with proficient mismatch repair (pMMR) CRC, who are microsatellite-stable (MSS) or have low levels of microsatellite instability (MSI-L). Here, we provide a comprehensive review on the immune microenvironment of CRC tumors and describe the rapid pace of scientific changes. We discuss the tremendous promise of cell-based immunotherapy strategies that are under preclinical studies/clinical trials or being u…