a 2022

Tumor infiltration of gamma-delta T cells in glioblastoma

JURÁŇ, Vilém, Martin PISKÁČEK, Marie TOMANDLOVÁ, Marek SOVA, Martin SMRČKA et. al.

Základní údaje

Originální název

Tumor infiltration of gamma-delta T cells in glioblastoma

Autoři

JURÁŇ, Vilém (203 Česká republika, domácí), Martin PISKÁČEK (40 Rakousko, domácí), Marie TOMANDLOVÁ (203 Česká republika, domácí), Marek SOVA (203 Česká republika, domácí), Martin SMRČKA (203 Česká republika, domácí), Tomáš KAZDA (203 Česká republika, domácí), Václav VYBÍHAL (203 Česká republika, domácí), Pavel FADRUS (203 Česká republika, domácí) a Andrea KNIGHT (203 Česká republika, garant, domácí)

Vydání

27th Annual Meeting and Education Day of the Society for Neuro-Oncology November 16 - 20, 2022, Tampa Convention Center, Tampa Bay, FL, 2022

Další údaje

Jazyk

angličtina

Typ výsledku

Konferenční abstrakt

Obor

30204 Oncology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Kód RIV

RIV/00216224:14110/22:00129713

Organizační jednotka

Lékařská fakulta

UT WoS

000888571000096

Klíčová slova anglicky

Tumor infiltration; gamma-delta T cells; glioblastoma

Štítky

Změněno: 27. 2. 2023 14:42, Mgr. Tereza Miškechová

Anotace

V originále

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.

Návaznosti

NV19-05-00410, projekt VaV
Název: Úloha cytotoxických gamma-delta T buněk na terapeutické rezistenci a recidivě Glioblastoma Multiforme
Investor: Ministerstvo zdravotnictví ČR, Úloha cytotoxických gamma-delta T buněk na terapeutické rezistenci a recidivě Glioblastoma Multiforme