We and others have demonstrated that IDH1R132H harbors an immunogenic neoepitope that is presented on MHC class II within glioma tissue, leads to spontaneous CD4+ T cell responses in some patients with recurrent IDH1R132H mutant gliomas detectable in peripheral blood, and can be targeted by peptide vaccination, which elicits a tumor-specific T helper cell response that is capable of controlling IDH1R132H-expressing tumors in an MHC-humanized preclinical model transgenic for the human MHC class II allele HLA-DR1 [19, 44, 45]. Here, HLA-C is linked to central nervous system cancer.