Early immune evasion in colorectal cancer: interplay between stem cells and the tumor microenvironment

Most colorectal cancers (CRCs) are characterized by a low mutational burden and an immune-cold microenvironment, limiting the efficacy of immune checkpoint blockade (ICB) therapies. While advanced tumors exhibit diverse immune evasion mechanisms, emerging evidence suggests that aspects of immune escape arise much earlier, within precancerous lesions. In this review, we discuss how early driver mutations and epigenetic alterations contribute to the establishment of an immunosuppressive microenvironment in CRC. We also highlight the dynamic crosstalk between cancer cells, stromal niche cells, and immune cells driving immune evasion and liver metastasis. A deeper understanding of these early events may guide the development of more effective preventive and therapeutic strategies for CRC.