These findings were supported by analyses of human GBM datasets, where high Fn14 expression correlated with immunosuppressive shifts and poor patient responses to immune checkpoint inhibitor therapy.<h4>Conclusions</h4>This study provides the first description of the contributions of both tumor- and host-derived Fn14 expression to tumor immunity and survival and identifies Fn14 as an important mediator of innate and adaptive immune responses in gliomas. This evidence concerns the gene TNFRSF12A and central nervous system cancer.