Infiltration of Gamma-delta T cells into Glioblastoma Tumor

JURÁŇ, Vilém, Barbora KOHLOVÁ, Martin PISKÁČEK, Vít ZMÁTLO, Leonard JAKUBÁČ, Veronika MOTÚZOVÁ, Marie TOMANDLOVÁ, Marek SOVA, Tomáš KAZDA, Václav VYBÍHAL, Pavel FADRUS and Andrea KNIGHT. Infiltration of Gamma-delta T cells into Glioblastoma Tumor. In WFNOS 2022 - the World Federation of Neuro-Oncology Societies (WFNOS), Seoul, South Korea. 2021.

Basic information

• Original name: Infiltration of Gamma-delta T cells into Glioblastoma Tumor
• Authors: JURÁŇ, Vilém, Barbora KOHLOVÁ, Martin PISKÁČEK, Vít ZMÁTLO, Leonard JAKUBÁČ, Veronika MOTÚZOVÁ, Marie TOMANDLOVÁ, Marek SOVA, Tomáš KAZDA, Václav VYBÍHAL, Pavel FADRUS and Andrea KNIGHT.
• Edition: WFNOS 2022 - the World Federation of Neuro-Oncology Societies (WFNOS), Seoul, South Korea, 2021.

Other information

• Original language: English
• Type of outcome: Conference abstract
• Confidentiality degree: is not subject to a state or trade secret
• Organization unit: Faculty of Medicine

Abstract

Gamma-delta (γδ) T cells are innate immunity effector lymphocytes with known prominent anti-tumor reactivity against aggressive glioblastoma (GBM). However, therapeutic approaches have had limited success due to the protective blood-brain-barrier and the immunosuppressive GBM tumor microenvironment. In this study, we determined Vδ1 a Vδ2 γδ T cell populations in peripheral blood and paired tumor tissue samples in patients (n=40) following the resection and throughtout the therapy follow-up. Tumor samples were processed using enzymatic kits and gentleMACSTM Dissociator (Miltenyi Biotec Inc.) and tumor-infiltrating γδ T lymphocytes (TILs) were analyzed by flow cytometry. We found infiltration of both intratumoral CD3+ γδ T cell subsets in 68% tumor samples. We detected Vδ1 γδ T cells in the range 0-0.8% (median 0.26%). Majority of GBM patients presented the Vδ2 subset among TILs in the range 0-13.8% (median 1.5%). Functional studies showed prominent cytotoxicity of magnetically sorted Vδ1 a Vδ2 γδ T cells against GBM cell lines and more importantly against primary tumors. Detailed phenotypic profiling and single-cell sequencing of Vδ2 γδ T cells is currently underway. Next, we identified the EphA2 receptor as one of the targets for tumor-reactive Vδ1 γδ T cells. Specifically, we found that blocking of EphA2 expression resulted in significant inhibition of GBM killing mediated by Vδ1 γδ T cells. Furthermore, multiplex analysis of soluble proteins in patients‘ plasma samples determined by Luminex® 200™ has identified significantly elevated levels of stress ligand MICA and check-point inhibitor ligands PD-L1 (B7-H1, CD274) and B7-H3 (CD276). The patient’s clinical course and therapeutic protocols will be discussed.

Links

• NV19-05-00410, research and development project: Name: Úloha cytotoxických gamma-delta T buněk na terapeutické rezistenci a recidivě Glioblastoma Multiforme

Investor: Ministry of Health of the CR