The Role of æ T-Lymphocytes in Glioblastoma: Current Trends and Future Directions

Cell-based immunotherapy for glioblastoma (GBM) encounters major challenges due to the infiltration-resistant and immunosuppressive tumor microenvironment (TME). gamma delta T cells, unconventional T cells expressing the characteristic gamma delta T cell receptor, have demonstrated promise in overcoming these challenges, suggesting great immunotherapeutic potential. This review presents the role of gamma delta T cells in GBM and proposes several research avenues for future studies. Using the PubMed, ScienceDirect, and JSTOR databases, we performed a review of the literature studying the biology of gamma delta T cells and their role in GBM treatment. We identified 15 studies focused on gamma delta T cells in human GBM. Infiltrative gamma delta T cells can incite antitumor immune responses in certain TMEs, though rapid tumor progression and TME hypoxia may impact the extent of tumor suppression. In the studies, available findings have shown both the potential for robust antitumor activity and the risk of protumor activity. While gamma delta T cells have potential as a therapeutic agent against GBM, the technical challenges of extracting, isolating, and expanding gamma delta T cells, and the activation of antitumoral versus protumoral cascades, remain barriers to their application. Overcoming these limitations may transform gamma delta T cells into a promising immunotherapy in GBM.