Tumor infiltration of gamma-delta T cells in glioblastoma

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Authors

JURÁŇ Vilém PISKÁČEK Martin TOMANDLOVÁ Marie SOVA Marek SMRČKA Martin KAZDA Tomáš VYBÍHAL Václav FADRUS Pavel KNIGHT Andrea

Year of publication 2022
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

Citation
Description Gamma-delta (??) 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 V?1 a V?2 ?? 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 ?? T lymphocytes (TILs) were analyzed by flow cytometry. We found infiltration of both intratumoral CD3+ ?? T cell subsets in 68% tumor samples. We detected V?1 ?? T cells in the range 0-0.8% (median 0.26%). Majority of GBM patients presented the V?2 subset among TILs in the range 0-13.8% (median 1.5%). Functional studies showed prominent cytotoxicity of magnetically sorted V?1 a V?2 ?? T cells against GBM cell lines and more importantly against primary tumors. Detailed phenotypic profiling and single-cell sequencing of V?2 ?? T cells is currently underway. Next, we identified the EphA2 receptor as one of the targets for tumor-reactive V?1 ?? T cells. Specifically, we found that blocking of EphA2 expression resulted in significant inhibition of GBM killing mediated by V?1 ?? T cells. Furthermore, Luminex xMAP technology identified significantly elevated levels of stress ligand MICA and check-point inhibitor ligands PD-L1 (B7-H1, CD274) and B7-H3 (CD276) and galectin-9 in patients‘ plasma samples at diagnosis compared to age-matched controls.
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