Moreover, we showed that ASCL2 induces an immune-excluded microenvironment by activating CAFs through transcriptional activation of TGFB secreted from cancer cells, paving the way for Wnt pathway or TGFB inhibitors combined with ICIs in pMMR/MSS CRCs, which presents a novel strategy and therapeutic opportunity (Fig. 7). Here, ASCL2 is linked to cancer.