Infiltration of Gamma-delta T cells into Glioblastoma Tumor

a 2021

Infiltration of Gamma-delta T cells into Glioblastoma Tumor

JURÁŇ, Vilém, Barbora KOHLOVÁ, Martin PISKÁČEK, Vít ZMÁTLO, Leonard JAKUBÁČ et. al.

Basic information

Original name

Infiltration of Gamma-delta T cells into Glioblastoma Tumor

Authors

Edition

WFNOS 2022 - the World Federation of Neuro-Oncology Societies (WFNOS), Seoul, South Korea, 2021

Other information

Language

English

Type of outcome

Konferenční abstrakt

Confidentiality degree

není předmětem státního či obchodního tajemství

Organization unit

Faculty of Medicine

Změněno: 26/1/2022 12:40, Mgr. Tereza Miškechová

Abstract

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, multiplex analysis of soluble proteins in patients‘ plasma samples determined by Luminex® 200™ has identified significantly elevated levels of stress ligand MICA and check-point inhibitor ligands PD-L1 (B7-H1, CD274) and B7-H3 (CD276). The patient’s clinical course and therapeutic protocols will be discussed.

Links

NV19-05-00410, research and development project

Name: Úloha cytotoxických gamma-delta T buněk na terapeutické rezistenci a recidivě Glioblastoma Multiforme

Investor: Ministry of Health of the CR

Citovat

JURÁŇ, Vilém, Barbora KOHLOVÁ, Martin PISKÁČEK, Vít ZMÁTLO, Leonard JAKUBÁČ, Veronika MOTÚZOVÁ, Marie TOMANDLOVÁ, Marek SOVA, Tomáš KAZDA, Václav VYBÍHAL, Pavel FADRUS and Andrea KNIGHT. Infiltration of Gamma-delta T cells into Glioblastoma Tumor. In WFNOS 2022 - the World Federation of Neuro-Oncology Societies (WFNOS), Seoul, South Korea. 2021.

@proceedings{1825203,
   author = {Juráň, Vilém and Kohlová, Barbora and Piskáček, Martin and Zmátlo, Vít and Jakubáč, Leonard and Motúzová, Veronika and Tomandlová, Marie and Sova, Marek and Kazda, Tomáš and Vybíhal, Václav and Fadrus, Pavel and Knight, Andrea},
   booktitle = {WFNOS 2022 - the World Federation of Neuro-Oncology Societies (WFNOS), Seoul, South Korea},
   language = {eng},
   title = {Infiltration of Gamma-delta T cells into Glioblastoma Tumor},
   year = {2021}
}

TY  - CONF
ID  - 1825203
AU  - Juráň, Vilém - Kohlová, Barbora - Piskáček, Martin - Zmátlo, Vít - Jakubáč, Leonard - Motúzová, Veronika - Tomandlová, Marie - Sova, Marek - Kazda, Tomáš - Vybíhal, Václav - Fadrus, Pavel - Knight, Andrea
PY  - 2021
TI  - Infiltration of Gamma-delta T cells into Glioblastoma Tumor
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, multiplex analysis of soluble proteins in patients‘ plasma samples determined by Luminex® 200™ has identified significantly elevated levels of stress ligand MICA and check-point inhibitor ligands PD-L1 (B7-H1, CD274) and B7-H3 (CD276). The patient’s clinical course and therapeutic protocols will be discussed.
ER  -

JURÁŇ, Vilém, Barbora KOHLOVÁ, Martin PISKÁČEK, Vít ZMÁTLO, Leonard JAKUBÁČ, Veronika MOTÚZOVÁ, Marie TOMANDLOVÁ, Marek SOVA, Tomáš KAZDA, Václav VYBÍHAL, Pavel FADRUS and Andrea KNIGHT. Infiltration of Gamma-delta T cells into Glioblastoma Tumor. In \textit{WFNOS 2022 - the World Federation of Neuro-Oncology Societies (WFNOS), Seoul, South Korea}. 2021.

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