Tumor-infiltrating lymphocytes (TILs) from patients with glioma

Tumor-infiltrating lymphocytes (TILs) may represent a viable source of T cells for the biological treatment of patients with gliomas. Glioma tissue was obtained from 16 patients, tumor cell lines were established, and TILs were expanded in 16/16 cases using a combination of IL-2/IL-15/IL-21. Intrace...

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Main Authors: Zhenjiang Liu, Qingda Meng, Jiri Bartek, Thomas Poiret, Oscar Persson, Lalit Rane, Elena Rangelova, Christopher Illies, Inti Harvey Peredo, Xiaohua Luo, Martin Vijayakumar Rao, Rebecca Axelsson Robertson, Ernest Dodoo, Markus Maeurer
Format: Article
Language:English
Published: Taylor & Francis Group 2017-02-01
Series:OncoImmunology
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Online Access:http://dx.doi.org/10.1080/2162402X.2016.1252894
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author Zhenjiang Liu
Qingda Meng
Jiri Bartek
Thomas Poiret
Oscar Persson
Lalit Rane
Elena Rangelova
Christopher Illies
Inti Harvey Peredo
Xiaohua Luo
Martin Vijayakumar Rao
Rebecca Axelsson Robertson
Ernest Dodoo
Markus Maeurer
author_facet Zhenjiang Liu
Qingda Meng
Jiri Bartek
Thomas Poiret
Oscar Persson
Lalit Rane
Elena Rangelova
Christopher Illies
Inti Harvey Peredo
Xiaohua Luo
Martin Vijayakumar Rao
Rebecca Axelsson Robertson
Ernest Dodoo
Markus Maeurer
author_sort Zhenjiang Liu
collection DOAJ
description Tumor-infiltrating lymphocytes (TILs) may represent a viable source of T cells for the biological treatment of patients with gliomas. Glioma tissue was obtained from 16 patients, tumor cell lines were established, and TILs were expanded in 16/16 cases using a combination of IL-2/IL-15/IL-21. Intracellular cytokine staining (ICS, IL-2, IL-17, TNFα and IFNγ production) as well as a cytotoxicity assay was used to detect TIL reactivity against autologous tumor cells or shared tumor-associated antigens (TAAs; i.e., NY-ESO-1, Survivin or EGFRvIII). TILs were analyzed by flow cytometry, including T-cell receptor (TCR) Vβ family composition, exhaustion/activation and T-cell differentiation markers (CD45RA/CCR7). IL-2/IL-15/IL-21 expanded TILs exhibited a mixture of CD4+, CD8+, as well as CD3+ CD4−CD8− T cells with a predominant central memory CD45RA−CCR7+ phenotype. TIL showed low frequencies of T cells testing positive for PD-1, TIM-3 and CTLA-4. LAG3 tested positive in up to 30% of CD8+ TIL, with low (1.25%) frequencies in CD4+ T cells. TIL cultures exhibited preferential usage of Vβ families and recognition of autologous tumor cells defined by cytokine production and cytotoxicity. IL-2/IL-15/IL-21 expanded TILs represent a viable source for the cellular therapy of patients with gliomas.
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spelling doaj.art-2989ff61d636499db67ae5e1461ad8252022-12-22T00:25:31ZengTaylor & Francis GroupOncoImmunology2162-402X2017-02-016210.1080/2162402X.2016.12528941252894Tumor-infiltrating lymphocytes (TILs) from patients with gliomaZhenjiang Liu0Qingda Meng1Jiri Bartek2Thomas Poiret3Oscar Persson4Lalit Rane5Elena Rangelova6Christopher Illies7Inti Harvey Peredo8Xiaohua Luo9Martin Vijayakumar Rao10Rebecca Axelsson Robertson11Ernest Dodoo12Markus Maeurer13Karolinska InstitutetKarolinska InstitutetKarolinska University HospitalKarolinska InstitutetKarolinska University HospitalKarolinska InstitutetIntervention and Technology, Karolinska HospitalKarolinska University HospitalKarolinska University HospitalKarolinska InstitutetKarolinska InstitutetKarolinska InstitutetKarolinska University HospitalKarolinska InstitutetTumor-infiltrating lymphocytes (TILs) may represent a viable source of T cells for the biological treatment of patients with gliomas. Glioma tissue was obtained from 16 patients, tumor cell lines were established, and TILs were expanded in 16/16 cases using a combination of IL-2/IL-15/IL-21. Intracellular cytokine staining (ICS, IL-2, IL-17, TNFα and IFNγ production) as well as a cytotoxicity assay was used to detect TIL reactivity against autologous tumor cells or shared tumor-associated antigens (TAAs; i.e., NY-ESO-1, Survivin or EGFRvIII). TILs were analyzed by flow cytometry, including T-cell receptor (TCR) Vβ family composition, exhaustion/activation and T-cell differentiation markers (CD45RA/CCR7). IL-2/IL-15/IL-21 expanded TILs exhibited a mixture of CD4+, CD8+, as well as CD3+ CD4−CD8− T cells with a predominant central memory CD45RA−CCR7+ phenotype. TIL showed low frequencies of T cells testing positive for PD-1, TIM-3 and CTLA-4. LAG3 tested positive in up to 30% of CD8+ TIL, with low (1.25%) frequencies in CD4+ T cells. TIL cultures exhibited preferential usage of Vβ families and recognition of autologous tumor cells defined by cytokine production and cytotoxicity. IL-2/IL-15/IL-21 expanded TILs represent a viable source for the cellular therapy of patients with gliomas.http://dx.doi.org/10.1080/2162402X.2016.1252894brain tumorcellular therapycytokinesgliomatil
spellingShingle Zhenjiang Liu
Qingda Meng
Jiri Bartek
Thomas Poiret
Oscar Persson
Lalit Rane
Elena Rangelova
Christopher Illies
Inti Harvey Peredo
Xiaohua Luo
Martin Vijayakumar Rao
Rebecca Axelsson Robertson
Ernest Dodoo
Markus Maeurer
Tumor-infiltrating lymphocytes (TILs) from patients with glioma
OncoImmunology
brain tumor
cellular therapy
cytokines
glioma
til
title Tumor-infiltrating lymphocytes (TILs) from patients with glioma
title_full Tumor-infiltrating lymphocytes (TILs) from patients with glioma
title_fullStr Tumor-infiltrating lymphocytes (TILs) from patients with glioma
title_full_unstemmed Tumor-infiltrating lymphocytes (TILs) from patients with glioma
title_short Tumor-infiltrating lymphocytes (TILs) from patients with glioma
title_sort tumor infiltrating lymphocytes tils from patients with glioma
topic brain tumor
cellular therapy
cytokines
glioma
til
url http://dx.doi.org/10.1080/2162402X.2016.1252894
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