Background: Colorectal cancer (CRC) is a common digestive tract malignancy with high incidence and mortality rates. Radiotherapy is the most common anti-tumor therapeutic regime and is frequently used for treating CRC, especially rectal cancer. However, radiotherapy can lead to tumor resistance to treatment. While previous research on radiotherapy resistance in CRC has mostly focused on the tumor itself, recent advances, especially the emergence of immunotherapy, have led to a greater emphasis on the immune microenvironment of the tumor. Summary: This review has summarized the recent literature on the role of the tumor immune microenvironment in CRC resistance to radiotherapy and provided new ideas for future anti-tumor treatment strategies. Key Messages: The proportion of immunosuppressive cells is greater than the numbers of cells associated with immune activation, leading to an overall state of immunosuppression; both the tumor and immunosuppressive cells secrete increased amounts of immunosuppressive regulatory factors, reduce the recognition and presentation of tumor antigens, inhibit immune cell’s anti-tumor effect, and offset the non-targeted anti-tumor effect of radiotherapy.

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