Fig. 6

Immune microenvironment regulates colorectal CSCs to drive tumor stemness. A CD4 + T cells secrete IL-22, which activates STAT3 in colorectal CSCs. The activation of STAT3 promotes the stemness of CRC and induces the expression of DOT1L, which promotes the expression of stemness-related genes by promoting H3K79me2 deposition at their promoter regions. B Treg cells act on colorectal CSCs by secreting IL-17 and promote the maintenance of CRC stemness through the AKT and MAPK signaling pathways. C CXCL1 secreted by tumor-associated dendritic cells (TADCs) promotes the expression of CD44 and CD133 and maintains the stemness of CRC. D Granulocyte myeloid-derived suppressor cells (G-MDSCs) secrete S100A9-containing exosomes that promote the stemness of colorectal CSCs by inducing STAT3 phosphorylation and NF-κB activation. E IL-1β secreted by tumor-associated macrophages (TAMs) inhibits the phosphorylation activation of GSK3β by activating the NF-κB and AKT signaling pathways, thereby abrogating the β-catenin destruction complex and activating the Wnt/β-catenin signaling pathway in colorectal CSCs