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With the advances in immunogenomics, the majority of tumor-specific antigens were found to be recognized by T helper cells (T H Cs). This observation led to the development of long epitope vaccines in various cancers. Mechanistically, we are still gaining a deeper understanding of the mode of action of T H Cs as precision antitumor agonists. Here, we discuss the specific cellular mechanisms of T H C functions in glioma immunology and contextualize current advances in anti-glioma vaccination exploiting T H Cs. [ABSTRACT FROM AUTHOR]

Mutation-specific vaccines have become increasingly important in glioma immunotherapy; however, shared neoepitopes are rare. For diffuse gliomas, a driver mutation in the gene for isocitrate dehydrogenase type-1 has been shown to produce an immunogenic epitope currently targeted in clinical trials. For highly aggressive midline gliomas, a recurrent point mutation in the histone-3 gene (H3F3A) causes an amino acid change from lysine to methionine at position 27 (K27M). Here, we demonstrate that a peptide vaccine against K27M-mutant histone-3 is capable of inducing effective, mutation-specific, cytotoxic T-cell- and T-helper-1-cell-mediated immune responses in a major histocompatibility complex (MHC)-humanized mouse model. By proving an immunologically effective presentation of the driver mutation H3K27M on MHC class II in human H3K27M-mutant gliomas, our data provide a basis for the further clinical development of vaccine-based or cell-based immunotherapeutic approaches targeting H3K27M. [ABSTRACT FROM PUBLISHER]