The Immunological Landscape of Colorectal Pre-Cancers: A Systematic Review

Colorectal cancer (CRC) develops predominantly through the adenoma-to-carcinoma sequence with immunological processes playing a central yet incompletely understood role in this progression. A systematic review was conducted of published academic literature using Medline, Embase, and Cochrane Library databases to identify studies which examined immune cell infiltration, cytokine profiling, and immune surveillance in colorectal pre-cancers. Studies published between October 1974 and July 2021 were included. Adaptive immune cells demonstrate dynamic infiltration patterns at various points along the adenoma-carcinoma sequence, with certain subsets of these lymphocytes facilitating tumor progression through immunosuppression while others confer protection. In contrast, innate immune cells demonstrate context-dependent roles in which pre-cancers may or may not develop into malignancies. Cytokine networks, particularly IL-6, IL-8, and IL-17, further modulate the tumor microenvironment. The immunological landscape of colorectal pre-cancers is complex, bidirectional, and non-linear in its relationships. Understanding these mechanisms provides a foundation for the development of immunologically informed prevention and early detection and intervention to mitigate CRC burden.