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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]