Noncanonical MAVS signaling restrains dendritic cell-driven antitumor immunity by inhibiting IL-12
MAVS-mediated cytosolic RNA sensing plays a central role in tumor immunogenicity. However, the effects of host MAVS signaling on antitumor immunity remains uncertain. Here, we demonstrate that host MAVS pathway drives accelerated tumor growth and impairs antitumor immunity, while MAVS knockout in dendritic cells (DCs) promotes tumor-reactive CD8+ T cell responses. Specifically, the CD8+ T cell priming capacity is enhanced by lack of functional MAVS in a type I interferon-independent, but IL-12-dependent, manner. Mechanistically, loss of RIG-I/MAVS cascade activates non-canonical NF-?B pathway and in turn induces IL-12 production by DCs, resulting in CD8+ T cell: DC crosstalk licensed by IFN-? and IL-12. Moreover, ablation of host MAVS sensitizes tumors to immunotherapy and attenuates radiation resistance, thereby facilitating the maintenance of effector CD8+ T cells. These findings identify that host MAVS pathway acts as an immune checkpoint of DC-driven antitumor immunity, indicating the development of DC-based immunotherapies through MAVS signaling antagonism. Overall design: To investigate the role of  the effects of host MAVS signaling on antitumor immunity, MC38 tumor cells were inoculated to WT and MAVS KO mice. Ten days after tumors inoculation, tumor infiltrated dendritic cells were isolated.Total RNA from each sample was extracted using Trizol Reagent following standard protocols and mRNA sequencing was performed.