Colorectal cancer (CRC) represents a major public health challenges, with one of the highest incidences worldwide. The two affected anatomical sites in CRC, i.e. the colon and the rectum, share important underlying features, but often differ in terms of therapeutic management. Current guidelines for CRC define its clinical stratification according to classical, tumor cell-based and pathological parameters. Novel ground-breaking findings in the recent years revealed the prominent role of the immune system in shaping CRC development. This chapter provides a detailed overview of the main genomic and immune features driving (or hampering) CRC progression, with a focus on the main immune cells and factors shaping its evolution. Furthermore, we discuss how tumor-infiltrating immunity could be leveraged both for therapeutic and stratification purposes.
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