Immune remodeling in inflammatory bowel disease-associated colorectal cancer: Mechanisms and immunotherapeutic implications (Review)

Abstract

Inflammatory bowel disease-associated colorectal cancer (IBD-CRC) arises in the setting of long-standing chronic intestinal inflammation, in which immune dysregulation cannot be readily attributed to the dominance of a single inhibitory pathway or to global immunosuppression. Persistent inflammatory signaling sustains a state of prolonged immune engagement, yet with constrained effector output, potentially compromising antitumor immune surveillance and limiting the clinical benefit of immunotherapy. The present review synthetises the accumulated knowledge on the long-term immunological alterations induced by chronic inflammation, including the integration of immune signaling, shifts in activation thresholds, metabolic reprogramming, and functional polarization of immune cells. These changes are discussed in the context of both tumor initiation and tumor maintenance to delineate the immunological evolution of IBD-CRC. The review further examines the relationship between inflammation-induced response constraints and the limited efficacy of immune checkpoint inhibitors, and summarizes the mechanistic barriers to immunotherapy in IBD-CRC. Collectively, these observations suggest that relieving inhibition through a single target may be insufficient to restore effective antitumor immunity. Finally, the potential value of natural plant-derived interventions characterized by multi-component, low-intensity, and long-term modulation is discussed, particularly with respect to reducing inflammatory burden and improving immune metabolic states, thereby providing a conceptual basis for the development of combination immunotherapeutic strategies.