Gamma-delta T cells in Glioblastoma patients

p 2021

Gamma-delta T cells in Glioblastoma patients

KOHLOVÁ, Barbora, Martin PISKÁČEK, Marie TOMANDLOVÁ, Veronika MOTÚZOVÁ, Vít ZMÁTLO et. al.

Základní údaje

Originální název

Gamma-delta T cells in Glioblastoma patients

Autoři

KOHLOVÁ, Barbora, Martin PISKÁČEK, Marie TOMANDLOVÁ, Veronika MOTÚZOVÁ, Vít ZMÁTLO, Vilém JURÁŇ, Marek SOVA, Václav VYBÍHAL, Pavel FADRUS, Tomáš KAZDA a Andrea KNIGHT

Vydání

The 9th International γδ T Cell Conference, 2021

Další údaje

Jazyk

angličtina

Typ výsledku

Vyžádané přednášky

Obor

30204 Oncology

Stát vydavatele

Čína

Utajení

není předmětem státního či obchodního tajemství

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

Gamma-delta T lymphocytes; Glioblastoma patients

Změněno: 21. 12. 2021 08:14, Mgr. Tereza Miškechová

Anotace

V originále

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.

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

Citovat

KOHLOVÁ, Barbora, Martin PISKÁČEK, Marie TOMANDLOVÁ, Veronika MOTÚZOVÁ, Vít ZMÁTLO, Vilém JURÁŇ, Marek SOVA, Václav VYBÍHAL, Pavel FADRUS, Tomáš KAZDA a Andrea KNIGHT. Gamma-delta T cells in Glioblastoma patients. In The 9th International γδ T Cell Conference. 2021.

@misc{1812897,
   author = {Kohlová, Barbora and Piskáček, Martin and Tomandlová, Marie and Motúzová, Veronika and Zmátlo, Vít and Juráň, Vilém and Sova, Marek and Vybíhal, Václav and Fadrus, Pavel and Kazda, Tomáš and Knight, Andrea},
   booktitle = {The 9th International γδ T Cell Conference},
   keywords = {Gamma-delta T lymphocytes; Glioblastoma patients},
   language = {eng},
   title = {Gamma-delta T cells in Glioblastoma patients},
   year = {2021}
}

TY  - SLIDE
ID  - 1812897
AU  - Kohlová, Barbora - Piskáček, Martin - Tomandlová, Marie - Motúzová, Veronika - Zmátlo, Vít - Juráň, Vilém - Sova, Marek - Vybíhal, Václav - Fadrus, Pavel - Kazda, Tomáš - Knight, Andrea
PY  - 2021
TI  - Gamma-delta T cells in Glioblastoma patients
KW  - Gamma-delta T lymphocytes
KW  - Glioblastoma patients
N2  - 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.
ER  -

KOHLOVÁ, Barbora, Martin PISKÁČEK, Marie TOMANDLOVÁ, Veronika MOTÚZOVÁ, Vít ZMÁTLO, Vilém JURÁŇ, Marek SOVA, Václav VYBÍHAL, Pavel FADRUS, Tomáš KAZDA a Andrea KNIGHT. Gamma-delta T cells in Glioblastoma patients. In \textit{The 9th International γδ T Cell Conference}. 2021.

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