Tumor infiltration of gamma-delta T cells in glioblastoma
| Autoři | |
|---|---|
| Rok publikování | 2022 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | 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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