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Subtype and grade-dependent spatial heterogeneity of T-cell infiltration in pediatric glioma

Brain tumors are the leading cause of cancer-related mortality in children and have distinct genomic and molecular features compared with adult glioma. However, the properties of immune cells in these tumors has been vastly understudied compared with their adult counterparts. We combined multiplex i...

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Autores principales: Robinson, M Hope, Vasquez, Juan, Kaushal, Akhilesh, MacDonald, Tobey J, Velázquez Vega, José E, Schniederjan, Matthew, Dhodapkar, Kavita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422651/
https://www.ncbi.nlm.nih.gov/pubmed/32788236
http://dx.doi.org/10.1136/jitc-2020-001066
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author Robinson, M Hope
Vasquez, Juan
Kaushal, Akhilesh
MacDonald, Tobey J
Velázquez Vega, José E
Schniederjan, Matthew
Dhodapkar, Kavita
author_facet Robinson, M Hope
Vasquez, Juan
Kaushal, Akhilesh
MacDonald, Tobey J
Velázquez Vega, José E
Schniederjan, Matthew
Dhodapkar, Kavita
author_sort Robinson, M Hope
collection PubMed
description Brain tumors are the leading cause of cancer-related mortality in children and have distinct genomic and molecular features compared with adult glioma. However, the properties of immune cells in these tumors has been vastly understudied compared with their adult counterparts. We combined multiplex immunofluorescence immunohistochemistry coupled with machine learning and single-cell mass cytometry to evaluate T-cells infiltrating pediatric glial tumors. We show that low-grade tumors are characterized by greater T-cell density compared with high-grade glioma (HGG). However, even among low-grade tumors, T-cell infiltration can be highly variable and subtype-dependent, with greater T-cell density in pleomorphic xanthoastrocytoma and ganglioglioma. CD3+ T-cell infiltration correlates inversely with the expression of SOX2, an embryonal stem cell marker commonly expressed by glial tumors. T-cells within both HGG and low-grade glioma (LGG) exhibit phenotypic heterogeneity and tissue-resident memory T-cells consist of distinct subsets of CD103+ and TCF1+ cells that exhibit distinct spatial localization patterns. TCF1+ T-cells are located closer to the vessels while CD103+ resident T-cells reside within the tumor further away from the vasculature. Recurrent tumors are characterized by a decline in CD103+ tumor-infiltrating T-cells. BRAF(V600E) mutation is immunogenic in children with LGG and may serve as a target for immune therapy. These data provide several novel insights into the subtype-dependent and grade-dependent changes in immune architecture in pediatric gliomas and suggest that harnessing tumor-resident T-cells may be essential to improve immune control in glioma.
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spelling pubmed-74226512020-08-19 Subtype and grade-dependent spatial heterogeneity of T-cell infiltration in pediatric glioma Robinson, M Hope Vasquez, Juan Kaushal, Akhilesh MacDonald, Tobey J Velázquez Vega, José E Schniederjan, Matthew Dhodapkar, Kavita J Immunother Cancer Clinical/Translational Cancer Immunotherapy Brain tumors are the leading cause of cancer-related mortality in children and have distinct genomic and molecular features compared with adult glioma. However, the properties of immune cells in these tumors has been vastly understudied compared with their adult counterparts. We combined multiplex immunofluorescence immunohistochemistry coupled with machine learning and single-cell mass cytometry to evaluate T-cells infiltrating pediatric glial tumors. We show that low-grade tumors are characterized by greater T-cell density compared with high-grade glioma (HGG). However, even among low-grade tumors, T-cell infiltration can be highly variable and subtype-dependent, with greater T-cell density in pleomorphic xanthoastrocytoma and ganglioglioma. CD3+ T-cell infiltration correlates inversely with the expression of SOX2, an embryonal stem cell marker commonly expressed by glial tumors. T-cells within both HGG and low-grade glioma (LGG) exhibit phenotypic heterogeneity and tissue-resident memory T-cells consist of distinct subsets of CD103+ and TCF1+ cells that exhibit distinct spatial localization patterns. TCF1+ T-cells are located closer to the vessels while CD103+ resident T-cells reside within the tumor further away from the vasculature. Recurrent tumors are characterized by a decline in CD103+ tumor-infiltrating T-cells. BRAF(V600E) mutation is immunogenic in children with LGG and may serve as a target for immune therapy. These data provide several novel insights into the subtype-dependent and grade-dependent changes in immune architecture in pediatric gliomas and suggest that harnessing tumor-resident T-cells may be essential to improve immune control in glioma. BMJ Publishing Group 2020-08-11 /pmc/articles/PMC7422651/ /pubmed/32788236 http://dx.doi.org/10.1136/jitc-2020-001066 Text en © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Clinical/Translational Cancer Immunotherapy
Robinson, M Hope
Vasquez, Juan
Kaushal, Akhilesh
MacDonald, Tobey J
Velázquez Vega, José E
Schniederjan, Matthew
Dhodapkar, Kavita
Subtype and grade-dependent spatial heterogeneity of T-cell infiltration in pediatric glioma
title Subtype and grade-dependent spatial heterogeneity of T-cell infiltration in pediatric glioma
title_full Subtype and grade-dependent spatial heterogeneity of T-cell infiltration in pediatric glioma
title_fullStr Subtype and grade-dependent spatial heterogeneity of T-cell infiltration in pediatric glioma
title_full_unstemmed Subtype and grade-dependent spatial heterogeneity of T-cell infiltration in pediatric glioma
title_short Subtype and grade-dependent spatial heterogeneity of T-cell infiltration in pediatric glioma
title_sort subtype and grade-dependent spatial heterogeneity of t-cell infiltration in pediatric glioma
topic Clinical/Translational Cancer Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422651/
https://www.ncbi.nlm.nih.gov/pubmed/32788236
http://dx.doi.org/10.1136/jitc-2020-001066
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