Gamma-delta T cells in Glioblastoma patients

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F21%3A00120151" target="_blank" >RIV/00216224:14110/21:00120151 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Gamma-delta T cells in Glioblastoma patients

Popis výsledku v původním jazyce

Gamma-delta (γδ) 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 γδ T lymphocytes (TILs) have not been extensively investigated.In this study, we examined Vδ1 a Vδ2 γδ 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 γδ T cells were analyzed by flow cytometry.We found infiltration of both intratumoral CD3+ γδ T cell subsets in 73% tested tumour samples. We detected Vδ1 γδ T cell in the range 0-0.5% (median 0.26%). Majority of GBM patients presented the Vδ2 subset among TILs in the range 0- 12% (median 3.2%). Functional studies showed prominent cytotoxicity of magnetically sorted Vδ1 a Vδ2 γδ 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 Vδ1 γδ T cells. Specifically, we found that blocking of EphA2 expression resulted in significant inhibition of GBM tumour killing mediated by Vδ1 γδ 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.

Název v anglickém jazyce

Gamma-delta T cells in Glioblastoma patients

Popis výsledku anglicky

Gamma-delta (γδ) 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 γδ T lymphocytes (TILs) have not been extensively investigated.In this study, we examined Vδ1 a Vδ2 γδ 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 γδ T cells were analyzed by flow cytometry.We found infiltration of both intratumoral CD3+ γδ T cell subsets in 73% tested tumour samples. We detected Vδ1 γδ T cell in the range 0-0.5% (median 0.26%). Majority of GBM patients presented the Vδ2 subset among TILs in the range 0- 12% (median 3.2%). Functional studies showed prominent cytotoxicity of magnetically sorted Vδ1 a Vδ2 γδ 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 Vδ1 γδ T cells. Specifically, we found that blocking of EphA2 expression resulted in significant inhibition of GBM tumour killing mediated by Vδ1 γδ 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.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30204 - Oncology

Projekt

<a href="/cs/project/NV19-05-00410" target="_blank" >NV19-05-00410: Úloha cytotoxických gamma-delta T buněk na terapeutické rezistenci a recidivě Glioblastoma Multiforme</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů