Fig. 3

dMMR/MSI facilitates immunotherapy through a pre-existing immunoreactive microenvironment. a dMMR/MSI facilitates immunotherapy through: upregulation of IFN-γ signaling; upregulation of MHCI/II and CXCL9/10/11; recruitment of immune cells; direct antiproliferative and pro-apoptotic effects of IFN-γ. b IFN-γ induces the expression of immune checkpoints including PD-L1, CTLA-4, LAG-3 and IDO, providing targets for ICB. c Silencing IFN-γ signaling to weaken PD-1-PD-L1 interactions helps improve potency of ACT monotherapy. While ICB could improve therapeutic efficacy of ACT through functional IFN-γ signaling. d Vaccination with dMMR/MSI-induced antigens could eliminate dMMR/MSI tumor cells and prevent outgrowth of undetected dMMR/MSI subclones