Figure 1.

The rectal tumor microenvironment. (a) Illustration representing the anatomy of the large intestine and the development of a tumor localized in the rectum. (b) The four consensus molecular subtypes and their specific stroma-immune microenvironments. CMS1 cluster displays strong immune activation with high levels of CD8⁺ T cells, CD4⁺ T cells, γδ T cells, activated dendritic cells (DCs), natural killer (NK) cells and M1 macrophages alongside high expression of cytokines, PD1, PD-L1 and MHC-I. CMS2 shows an immune-desert microenvironment characterized by a few immune cells and poor expression of PD1, PD-L1, LAG-3 and CTLA-4. CMS3 is distinguished by metabolic dysregulation, infiltration of Th17 cells, naive B and T cells, and expression of MHC-I, PD1 and PD-L1. CMS4 exhibits high angiogenesis activity, expression of TGF-β, and infiltration of CD8⁺ T cells, CD4⁺ T cells, Tregs, M2 macrophages, monocytes, eosinophils and resting DCs.