Genomic, Microbial and Immunological Microenvironment of Colorectal Polyps

SIMPLE SUMMARY: Colorectal cancers (CRC) initiate from small cell clusters known as polyps. Colonoscopic surveillance and removal of polyps is an important strategy to prevent CRC progression. Recent advances in sequencing technologies have highlighted genetic mutations in polyps that potentially contribute to CRC development. However, CRC might be considered more than a genetic disease, as emerging evidence describes early changes to immune surveillance and gut microbiota in people with polyps. Here, we review the molecular landscape of colorectal polyps, considering their genomic, microbial and immunological features, and discuss the potential clinical utility of these data. ABSTRACT: Colorectal cancer (CRC) develops from pre-cancerous cellular lesions in the gut epithelium, known as polyps. Polyps themselves arise through the accumulation of mutations that disrupt the function of key tumour suppressor genes, activate proto-oncogenes and allow proliferation in an environment where immune control has been compromised. Consequently, colonoscopic surveillance and polypectomy are central pillars of cancer control strategies. Recent advances in genomic sequencing technologies have enhanced our knowledge of key driver mutations in polyp lesions that likely contribute to CRC. In accordance with the prognostic significance of Immunoscores for CRC survival, there is also a likely role for early immunological changes in polyps, including an increase in regulatory T cells and a decrease in mature dendritic cell numbers. Gut microbiotas are under increasing research interest for their potential contribution to CRC evolution, and changes in the gut microbiome have been reported from analyses of adenomas. Given that early changes to molecular components of bowel polyps may have a direct impact on cancer development and/or act as indicators of early disease, we review the molecular landscape of colorectal polyps, with an emphasis on immunological and microbial alterations occurring in the gut and propose the potential clinical utility of these data.