Gamma-delta T cells in Glioblastoma patients
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| Year of publication | 2021 |
| MU Faculty or unit | |
| Citation | |
| Description | Gamma-delta (??) T cells are important effector lymphocytes of innate immunity with proven antitumour reactivity against aggressive glioblastoma brain tumour (GBM). Therapeutic approaches to GBM have had limited success particularly due to the protective brain barrier and the tumour immunosuppressive microenvironment. The GBM-infiltrating ?? T lymphocytes (TILs) have not been extensively investigated.In this study, we examined V?1 a V?2 ?? T cell populations in peripheral blood and paired tumour tissue samples from GBM patients (n=33) following the resection and throughtout the therapy follow-up. Tumour samples were processed using enzymatic kits and gentleMACSTM Dissociator (Miltenyi Biotec Inc.) and TIL ?? T cells were analyzed by flow cytometry.We found infiltration of both intratumoral CD3+ ?? T cell subsets in 73% tested tumour samples. We detected V?1 ?? T cell in the range 0-0.5% (median 0.26%). Majority of GBM patients presented the V?2 subset among TILs in the range 0- 12% (median 3.2%). Functional studies showed prominent cytotoxicity of magnetically sorted V?1 a V?2 ?? T cells against GBM cell lines and more importantly against primary tumours. Next, we identified the EphA2 receptor as one of the targets for tumour reactive V?1 ?? T cells. Specifically, we found that blocking of EphA2 expression resulted in significant inhibition of GBM tumour killing mediated by V?1 ?? T cells. Furthermore, multiplex analysis of soluble proteins by Luminex® 200™ in patients‘ plasma samples identified significantly elevated levels of MICA, check-point inhibitors B7-H3 (CD276), PD-L1 (B7-H1, CD274), Galectin-9 and Nectin-4. The patient’s clinical course, therapeutic protocols and RNAseq data will be discussed. |
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