γδ T cells as a potential therapeutic agent for glioblastoma

Front Immunol. 2023 Oct 20:14:1273986. doi: 10.3389/fimmu.2023.1273986. eCollection 2023.

Abstract

Although γδ T cells comprise a small population of T cells, they perform important roles in protecting against infection and suppressing tumors. With their distinct tissue-localizing properties, combined with their various target recognition mechanisms, γδ T cells have the potential to become an effective solution for tumors that do not respond to current therapeutic procedures. One such tumor, glioblastoma (GBM), is a malignant brain tumor with the highest World Health Organization grade and therefore the worst prognosis. The immune-suppressive tumor microenvironment (TME) and immune-evasive glioma stem cells are major factors in GBM immunotherapy failure. Currently, encouraged by the strong anti-tumoral function of γδ T cells revealed at the preclinical and clinical levels, several research groups have shown progression of γδ T cell-based GBM treatment. However, several limitations still exist that block effective GBM treatment using γδ T cells. Therefore, understanding the distinct roles of γδ T cells in anti-tumor immune responses and the suppression mechanism of the GBM TME are critical for successful γδ T cell-mediated GBM therapy. In this review, we summarize the effector functions of γδ T cells in tumor immunity and discuss current advances and limitations of γδ T cell-based GBM immunotherapy. Additionally, we suggest future directions to overcome the limitations of γδ T cell-based GBM immunotherapy to achieve successful treatment of GBM.

Keywords: engineering; glioblastoma; immunotherapy; tumor microenvironment; γδ T cells.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms*
  • Glioblastoma*
  • Humans
  • Immunotherapy / methods
  • Intraepithelial Lymphocytes* / pathology
  • Receptors, Antigen, T-Cell, gamma-delta
  • Tumor Microenvironment

Substances

  • Receptors, Antigen, T-Cell, gamma-delta

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Research Foundation of Korea (NRF-2021M3A9H3015688 and NRF-2021M3A9D3026428) funded by the Ministry of Science and ICT of Korea. This work was also supported by the Samsung Science and Technology Foundation (SSTF-BA1902-05), Republic of Korea.