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...
Main Authors: | , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Taylor & Francis Group
2017-02-01
|
Series: | OncoImmunology |
Subjects: | |
Online Access: | http://dx.doi.org/10.1080/2162402X.2016.1252894 |
_version_ | 1818234695887880192 |
---|---|
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. |
first_indexed | 2024-12-12T11:42:10Z |
format | Article |
id | doaj.art-2989ff61d636499db67ae5e1461ad825 |
institution | Directory Open Access Journal |
issn | 2162-402X |
language | English |
last_indexed | 2024-12-12T11:42:10Z |
publishDate | 2017-02-01 |
publisher | Taylor & Francis Group |
record_format | Article |
series | OncoImmunology |
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 |
work_keys_str_mv | AT zhenjiangliu tumorinfiltratinglymphocytestilsfrompatientswithglioma AT qingdameng tumorinfiltratinglymphocytestilsfrompatientswithglioma AT jiribartek tumorinfiltratinglymphocytestilsfrompatientswithglioma AT thomaspoiret tumorinfiltratinglymphocytestilsfrompatientswithglioma AT oscarpersson tumorinfiltratinglymphocytestilsfrompatientswithglioma AT lalitrane tumorinfiltratinglymphocytestilsfrompatientswithglioma AT elenarangelova tumorinfiltratinglymphocytestilsfrompatientswithglioma AT christopherillies tumorinfiltratinglymphocytestilsfrompatientswithglioma AT intiharveyperedo tumorinfiltratinglymphocytestilsfrompatientswithglioma AT xiaohualuo tumorinfiltratinglymphocytestilsfrompatientswithglioma AT martinvijayakumarrao tumorinfiltratinglymphocytestilsfrompatientswithglioma AT rebeccaaxelssonrobertson tumorinfiltratinglymphocytestilsfrompatientswithglioma AT ernestdodoo tumorinfiltratinglymphocytestilsfrompatientswithglioma AT markusmaeurer tumorinfiltratinglymphocytestilsfrompatientswithglioma |