Emerging Complexity in CD4+T Lineage Programming and Its Implications in Colorectal Cancer

The intestinal immune system has the difficult task of protecting a large environmentally exposed single layer of epithelium from pathogens without allowing inappropriate inflammatory responses. Unmitigated inflammation drives multiple pathologies, including the development of colorectal cancer. CD4(+)T cells mediate both the suppression and promotion of intestinal inflammation. They comprise an array of phenotypically and functionally distinct subsets tailored to a specific inflammatory context. This diversity of form and function is relevant to a broad array of pathologic and physiologic processes. The heterogeneity underlying both effector and regulatory T helper cell responses to colorectal cancer, and its impact on disease progression, is reviewed herein. Importantly, T cell responses are dynamic; they exhibit both quantitative and qualitative changes as the inflammatory context shifts. Recent evidence outlines the role of CD4(+)T cells in colorectal cancer responses and suggests possible mechanisms driving qualitative alterations in anti-cancer immune responses. The heterogeneity of T cells in colorectal cancer, as well as the manner and mechanism by which they change, offer an abundance of opportunities for more specific, and likely effective, interventional strategies.

Automated summary

The intestinal immune system plays a crucial role in protecting the epithelial layer from pathogens and inflammation, which could lead to diseases such as colorectal cancer. CD4(+)T cells have a diverse range of functions in regulating intestinal inflammation, including both suppression and promotion. The heterogeneity of CD4(+)T cells in colorectal cancer and their dynamic responses offer potential opportunities for targeted intervention strategies.