Immunologic Drivers and Restraints in Colitis-Associated Colorectal Cancer

Inflammatory bowel diseases (IBD), encompassing ulcerative colitis and Crohn’s dis-ease, are associated with an increased risk of colorectal cancer through mechanisms driven by persistent mucosal inflammation. Chronic inflammatory signaling, recurrent epithelial injury, and altered tissue repair processes progressively reshape the intesti-nal microenvironment, promoting genomic instability and facilitating the development of colitis-associated colorectal cancer (CAC). Despite the well-established link between inflammation and tumorigenesis, only a subset of patients with long-standing IBD de-velops malignancy, highlighting the complexity of the regulatory effects of the ongoing inflammation on the tumor initiation and progression. This review discusses the multifaceted roles of innate and adaptive immune responses in CAC pathogenesis. Innate immune signaling mediated by pattern recognition recep-tors, particularly Toll-like receptors, integrates microbial and damage-associated sig-nals to activate inflammatory pathways that regulate epithelial proliferation, survival, and tumor-promoting cytokine networks. Tumor-associated macrophages, neutrophils, and myeloid-derived suppressor cells contribute to carcinogenesis by sustaining chronic inflammation, promoting immunosuppression, and remodeling the tumor mi-croenvironment, although under specific conditions these cells can also support anti-tumor immunity. Innate lymphocyte subsets participate in immune surveillance and epithelial homeostasis, yet may also amplify inflammatory circuits that influence tu-mor development. Adaptive immune populations further shape CAC evolution, as CD4⁺ T-helper subsets, CD8⁺ cytotoxic T lymphocytes, regulatory T cells, and B cells exert divergent effects depending on cytokine milieu, immune context, and disease stage. Understanding immune-cell plasticity and the molecular pathways governing these processes may facilitate the identification of predictive biomarkers and the de-velopment of targeted immunomodulatory strategies aimed at preventing CAC.