γδ T Cells in Glioblastoma Multiforme: Novel Roles and Therapeutic Opportunities

Abstract

Glioblastoma multiforme (GBM) is one of the most aggressive cancers, with limited treatment options due to its highly immunosuppressive microenvironment and resistance to conventional therapies. gamma delta T cells, known for their potent antitumor activity and ability to recognize tumor antigens independently of HLA molecules, have emerged as a promising therapeutic strategy. This review explores the role of gamma delta T cells in glioblastoma, focusing on their functional plasticity, cytotoxic mechanisms, and interactions with components of the tumor microenvironment. We examine the factors that influence gamma delta T cell polarization toward pro- or anti-tumor phenotypes and analyze preclinical findings that support their application in GBM treatment. Furthermore, we discuss potential combinatory approaches-including immune checkpoint inhibitors, cytokine stimulation, and adoptive cell transfer techniques-to enhance the therapeutic effectiveness and persistence of gamma delta T cells. Understanding the dynamics between GBM and gamma delta T cells may pave the way for innovative immunotherapeutic strategies aimed at overcoming immune evasion and improving clinical outcomes.