JURÁŇ, Vilém, Martin PISKÁČEK, Marie TOMANDLOVÁ, Marek SOVA, Martin SMRČKA, Tomáš KAZDA, Václav VYBÍHAL, Pavel FADRUS a Andrea KNIGHT. Tumor infiltration of gamma-delta T cells in glioblastoma. In 27th Annual Meeting and Education Day of the Society for Neuro-Oncology November 16 - 20, 2022, Tampa Convention Center, Tampa Bay, FL. 2022. |
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@proceedings{2235677, author = {Juráň, Vilém and Piskáček, Martin and Tomandlová, Marie and Sova, Marek and Smrčka, Martin and Kazda, Tomáš and Vybíhal, Václav and Fadrus, Pavel and Knight, Andrea}, booktitle = {27th Annual Meeting and Education Day of the Society for Neuro-Oncology November 16 - 20, 2022, Tampa Convention Center, Tampa Bay, FL}, keywords = {Tumor infiltration; gamma-delta T cells; glioblastoma}, language = {eng}, title = {Tumor infiltration of gamma-delta T cells in glioblastoma}, year = {2022} }
TY - CONF ID - 2235677 AU - Juráň, Vilém - Piskáček, Martin - Tomandlová, Marie - Sova, Marek - Smrčka, Martin - Kazda, Tomáš - Vybíhal, Václav - Fadrus, Pavel - Knight, Andrea PY - 2022 TI - Tumor infiltration of gamma-delta T cells in glioblastoma KW - Tumor infiltration KW - gamma-delta T cells KW - glioblastoma N2 - 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, 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. ER -
JURÁŇ, Vilém, Martin PISKÁČEK, Marie TOMANDLOVÁ, Marek SOVA, Martin SMRČKA, Tomáš KAZDA, Václav VYBÍHAL, Pavel FADRUS a Andrea KNIGHT. Tumor infiltration of gamma-delta T cells in glioblastoma. In \textit{27th Annual Meeting and Education Day of the Society for Neuro-Oncology November 16 - 20, 2022, Tampa Convention Center, Tampa Bay, FL}. 2022.
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