Analysis of the Effectiveness of Glioma Immunotherapy Using Gamma-Delta T Lymphocytes – Glejak

The glioblastoma multiforme (GBM) is the most common malignant brain tumor with a very poor prognosis and a median survival of approximately 10 months. Current treatment methods, including surgery, radiotherapy, and chemotherapy, show low efficacy, as tumor cells survive in about 90% of cases. These statistics highlight the urgent need for more effective therapeutic approaches in GBM treatment.

A promising direction in oncology is immunotherapy—a therapeutic approach that harnesses the body’s own immune cells to recognize and eliminate cancer cells. Among immune cells with anti-tumor potential, a particularly interesting group are T lymphocytes possessing a T cell receptor (TCR) composed of γ and δ chains, known as γδ T cells.

In humans, two major γδ T cell populations are recognized:

• Vδ2+ cells, predominant in peripheral blood, and

• Vδ1+ cells, found mainly in peripheral tissues.

Both populations can recognize tumor-associated and stress-induced antigens, enabling them to mount a cytotoxic response against cancer cells. So far, preclinical studies using mouse models of GBM have successfully tested Vδ2+ cells expanded in vitro, but these experiments lacked a human tumor microenvironment—including patient-derived immune cells that can suppress anti-tumor responses.

This project aims to compare the effector functions of Vδ1+ and Vδ2+ γδ T cells against glioma cells to determine which population holds the greatest therapeutic potential for immunotherapy.

Through collaboration with neurosurgeons from the Wroclaw Medical University, glioma tissue samples resected from patients will be used to characterize the cytotoxic activity of γδ T cells in vitro and in vivo. The in vivo studies will employ humanized mouse models, which better replicate the human tumor microenvironment, allowing more accurate assessment of γδ T cell-based therapies.

The results of this project are expected to advance the understanding of γδ T cell functions in glioma and may contribute to the development of novel, effective immunotherapeutic strategies for treating glioblastoma multiforme (GBM).