Fig. 5

CSC-intrinsic immune factors in CSC-immune cell crosstalk. A PD-L1 interacts with Frizzled 6 to inhibit the degradation of β-catenin via the destruction complex. Moreover, the activation of the Wnt/β-catenin pathway induces the expression of PD-L1, forming a positive feedback β-catenin/PD-L1 loop to promote the stemness and expansion of colorectal CSCs. B PD-L1 interacts with the HMGA1 to promote the proliferation of colorectal CSCs by activating the HMGA1-dependent MEK/ERK and AKT signaling pathways. C Colorectal CSCs express low levels of S100A14 (SA14) to avoid the degradation of STAT3 in CSCs, and thus PD-L1 is highly expressed as a target of STAT3. D circREEP3 recruits the chromatin-remodeling protein CHD7 to the promoter of FKBP10 to activate its transcription and promote tumor progression. In addition, circREEP3 can enhance the ubiquitination and degradation of RIG-1 mediated by RNF125, thereby inhibiting antitumor immune effects