Unveiling the tumor microenvironment in colorectal cancer therapeutic resistance

Therapeutic resistance remains a major barrier to effective treatment in colorectal cancer (CRC), where the tumor microenvironment (TME) plays a pivotal role in modulating responses to chemotherapy, immunotherapy, and targeted therapies. This review synthesizes current evidence on how cellular and non-cellular TME components contribute to resistance mechanisms in CRC. Key immune cells, including T cells, macrophages, neutrophils, natural killer cells, dendritic cells, and myeloid-derived suppressor cells, orchestrate immunosuppressive networks that impair drug efficacy. For instance, regulatory T cells and M2-polarized macrophages promote chemoresistance via cytokine secretion and metabolic reprogramming,…