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Characterising Distinct Migratory Profiles of Infiltrating T-Cell Subsets in Human Glioblastoma

Glioblastoma is the most common and aggressive form of primary brain cancer, with no improvements in the 5-year survival rate of 4.6% over the past three decades. T-cell-based immunotherapies such as immune-checkpoint inhibitors and chimeric antigen receptor T-cell therapy have prolonged the surviva...

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Autores principales: Kollis, Paris M., Ebert, Lisa M., Toubia, John, Bastow, Cameron R., Ormsby, Rebecca J., Poonnoose, Santosh I., Lenin, Sakthi, Tea, Melinda N., Pitson, Stuart M., Gomez, Guillermo A., Brown, Michael P., Gargett, Tessa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019231/
https://www.ncbi.nlm.nih.gov/pubmed/35464424
http://dx.doi.org/10.3389/fimmu.2022.850226
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author Kollis, Paris M.
Ebert, Lisa M.
Toubia, John
Bastow, Cameron R.
Ormsby, Rebecca J.
Poonnoose, Santosh I.
Lenin, Sakthi
Tea, Melinda N.
Pitson, Stuart M.
Gomez, Guillermo A.
Brown, Michael P.
Gargett, Tessa
author_facet Kollis, Paris M.
Ebert, Lisa M.
Toubia, John
Bastow, Cameron R.
Ormsby, Rebecca J.
Poonnoose, Santosh I.
Lenin, Sakthi
Tea, Melinda N.
Pitson, Stuart M.
Gomez, Guillermo A.
Brown, Michael P.
Gargett, Tessa
author_sort Kollis, Paris M.
collection PubMed
description Glioblastoma is the most common and aggressive form of primary brain cancer, with no improvements in the 5-year survival rate of 4.6% over the past three decades. T-cell-based immunotherapies such as immune-checkpoint inhibitors and chimeric antigen receptor T-cell therapy have prolonged the survival of patients with other cancers and have undergone early-phase clinical evaluation in glioblastoma patients. However, a major challenge for T-cell-based immunotherapy of glioblastoma and other solid cancers is T-cell infiltration into tumours. This process is mediated by chemokine-chemokine receptor and integrin-adhesion molecule interactions, yet the specific nature of the molecules that may facilitate T-cell homing into glioblastoma are unknown. Here, we have characterised chemokine receptor and integrin expression profiles of endogenous glioblastoma-infiltrating T cells, and the chemokine expression profile of glioblastoma-associated cells, by single-cell RNA-sequencing. Subsequently, chemokine receptors and integrins were validated at the protein level to reveal enrichment of receptors CCR2, CCR5, CXCR3, CXCR4, CXCR6, CD49a, and CD49d in glioblastoma-infiltrating T-cell populations relative to T cells in matched patient peripheral blood. Complementary chemokine ligand expression was then validated in glioblastoma biopsies and glioblastoma-derived primary cell cultures. Together, enriched expression of homing receptor-ligand pairs identified in this study implicate a potential role in mediating T-cell infiltration into glioblastoma. Importantly, our data characterising the migratory receptors on endogenous tumour-infiltrating T cells could be exploited to enhance the tumour-homing properties of future T-cell immunotherapies for glioblastoma.
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spelling pubmed-90192312022-04-21 Characterising Distinct Migratory Profiles of Infiltrating T-Cell Subsets in Human Glioblastoma Kollis, Paris M. Ebert, Lisa M. Toubia, John Bastow, Cameron R. Ormsby, Rebecca J. Poonnoose, Santosh I. Lenin, Sakthi Tea, Melinda N. Pitson, Stuart M. Gomez, Guillermo A. Brown, Michael P. Gargett, Tessa Front Immunol Immunology Glioblastoma is the most common and aggressive form of primary brain cancer, with no improvements in the 5-year survival rate of 4.6% over the past three decades. T-cell-based immunotherapies such as immune-checkpoint inhibitors and chimeric antigen receptor T-cell therapy have prolonged the survival of patients with other cancers and have undergone early-phase clinical evaluation in glioblastoma patients. However, a major challenge for T-cell-based immunotherapy of glioblastoma and other solid cancers is T-cell infiltration into tumours. This process is mediated by chemokine-chemokine receptor and integrin-adhesion molecule interactions, yet the specific nature of the molecules that may facilitate T-cell homing into glioblastoma are unknown. Here, we have characterised chemokine receptor and integrin expression profiles of endogenous glioblastoma-infiltrating T cells, and the chemokine expression profile of glioblastoma-associated cells, by single-cell RNA-sequencing. Subsequently, chemokine receptors and integrins were validated at the protein level to reveal enrichment of receptors CCR2, CCR5, CXCR3, CXCR4, CXCR6, CD49a, and CD49d in glioblastoma-infiltrating T-cell populations relative to T cells in matched patient peripheral blood. Complementary chemokine ligand expression was then validated in glioblastoma biopsies and glioblastoma-derived primary cell cultures. Together, enriched expression of homing receptor-ligand pairs identified in this study implicate a potential role in mediating T-cell infiltration into glioblastoma. Importantly, our data characterising the migratory receptors on endogenous tumour-infiltrating T cells could be exploited to enhance the tumour-homing properties of future T-cell immunotherapies for glioblastoma. Frontiers Media S.A. 2022-04-06 /pmc/articles/PMC9019231/ /pubmed/35464424 http://dx.doi.org/10.3389/fimmu.2022.850226 Text en Copyright © 2022 Kollis, Ebert, Toubia, Bastow, Ormsby, Poonnoose, Lenin, Tea, Pitson, Gomez, Brown and Gargett https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Kollis, Paris M.
Ebert, Lisa M.
Toubia, John
Bastow, Cameron R.
Ormsby, Rebecca J.
Poonnoose, Santosh I.
Lenin, Sakthi
Tea, Melinda N.
Pitson, Stuart M.
Gomez, Guillermo A.
Brown, Michael P.
Gargett, Tessa
Characterising Distinct Migratory Profiles of Infiltrating T-Cell Subsets in Human Glioblastoma
title Characterising Distinct Migratory Profiles of Infiltrating T-Cell Subsets in Human Glioblastoma
title_full Characterising Distinct Migratory Profiles of Infiltrating T-Cell Subsets in Human Glioblastoma
title_fullStr Characterising Distinct Migratory Profiles of Infiltrating T-Cell Subsets in Human Glioblastoma
title_full_unstemmed Characterising Distinct Migratory Profiles of Infiltrating T-Cell Subsets in Human Glioblastoma
title_short Characterising Distinct Migratory Profiles of Infiltrating T-Cell Subsets in Human Glioblastoma
title_sort characterising distinct migratory profiles of infiltrating t-cell subsets in human glioblastoma
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019231/
https://www.ncbi.nlm.nih.gov/pubmed/35464424
http://dx.doi.org/10.3389/fimmu.2022.850226
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