Enhancing T Cell Chemotaxis and Infiltration in Glioblastoma

Glioblastoma is an immunologically ‘cold’ tumor, which are characterized by absent or minimal numbers of tumor-infiltrating lymphocytes (TILs). For those tumors that have been invaded by lymphocytes, they are profoundly exhausted and ineffective. While many immunotherapy approaches seek to reinvigor...

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Autores principales:	Kirit Singh, Kelly M. Hotchkiss, Kisha K. Patel, Daniel S. Wilkinson, Aditya A. Mohan, Sarah L. Cook, John H. Sampson
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	immunotherapy glioblastoma blood–brain barrier central nervous system T cells T lymphocytes Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/8aef5234162f41c9be3e1d253db29419
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spelling	oai:doaj.org-article:8aef5234162f41c9be3e1d253db294192021-11-11T15:29:19ZEnhancing T Cell Chemotaxis and Infiltration in Glioblastoma10.3390/cancers132153672072-6694https://doaj.org/article/8aef5234162f41c9be3e1d253db294192021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5367https://doaj.org/toc/2072-6694Glioblastoma is an immunologically ‘cold’ tumor, which are characterized by absent or minimal numbers of tumor-infiltrating lymphocytes (TILs). For those tumors that have been invaded by lymphocytes, they are profoundly exhausted and ineffective. While many immunotherapy approaches seek to reinvigorate immune cells at the tumor, this requires TILs to be present. Therefore, to unleash the full potential of immunotherapy in glioblastoma, the trafficking of lymphocytes to the tumor is highly desirable. However, the process of T cell recruitment into the central nervous system (CNS) is tightly regulated. Naïve T cells may undergo an initial licensing process to enter the migratory phenotype necessary to enter the CNS. T cells then must express appropriate integrins and selectin ligands to interact with transmembrane proteins at the blood–brain barrier (BBB). Finally, they must interact with antigen-presenting cells and undergo further licensing to enter the parenchyma. These T cells must then navigate the tumor microenvironment, which is rich in immunosuppressive factors. Altered tumoral metabolism also interferes with T cell motility. In this review, we will describe these processes and their mediators, along with potential therapeutic approaches to enhance trafficking. We also discuss safety considerations for such approaches as well as potential counteragents.Kirit SinghKelly M. HotchkissKisha K. PatelDaniel S. WilkinsonAditya A. MohanSarah L. CookJohn H. SampsonMDPI AGarticleimmunotherapyglioblastomablood–brain barriercentral nervous systemT cellsT lymphocytesNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5367, p 5367 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	immunotherapy glioblastoma blood–brain barrier central nervous system T cells T lymphocytes Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	immunotherapy glioblastoma blood–brain barrier central nervous system T cells T lymphocytes Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Kirit Singh Kelly M. Hotchkiss Kisha K. Patel Daniel S. Wilkinson Aditya A. Mohan Sarah L. Cook John H. Sampson Enhancing T Cell Chemotaxis and Infiltration in Glioblastoma
description	Glioblastoma is an immunologically ‘cold’ tumor, which are characterized by absent or minimal numbers of tumor-infiltrating lymphocytes (TILs). For those tumors that have been invaded by lymphocytes, they are profoundly exhausted and ineffective. While many immunotherapy approaches seek to reinvigorate immune cells at the tumor, this requires TILs to be present. Therefore, to unleash the full potential of immunotherapy in glioblastoma, the trafficking of lymphocytes to the tumor is highly desirable. However, the process of T cell recruitment into the central nervous system (CNS) is tightly regulated. Naïve T cells may undergo an initial licensing process to enter the migratory phenotype necessary to enter the CNS. T cells then must express appropriate integrins and selectin ligands to interact with transmembrane proteins at the blood–brain barrier (BBB). Finally, they must interact with antigen-presenting cells and undergo further licensing to enter the parenchyma. These T cells must then navigate the tumor microenvironment, which is rich in immunosuppressive factors. Altered tumoral metabolism also interferes with T cell motility. In this review, we will describe these processes and their mediators, along with potential therapeutic approaches to enhance trafficking. We also discuss safety considerations for such approaches as well as potential counteragents.
format	article
author	Kirit Singh Kelly M. Hotchkiss Kisha K. Patel Daniel S. Wilkinson Aditya A. Mohan Sarah L. Cook John H. Sampson
author_facet	Kirit Singh Kelly M. Hotchkiss Kisha K. Patel Daniel S. Wilkinson Aditya A. Mohan Sarah L. Cook John H. Sampson
author_sort	Kirit Singh
title	Enhancing T Cell Chemotaxis and Infiltration in Glioblastoma
title_short	Enhancing T Cell Chemotaxis and Infiltration in Glioblastoma
title_full	Enhancing T Cell Chemotaxis and Infiltration in Glioblastoma
title_fullStr	Enhancing T Cell Chemotaxis and Infiltration in Glioblastoma
title_full_unstemmed	Enhancing T Cell Chemotaxis and Infiltration in Glioblastoma
title_sort	enhancing t cell chemotaxis and infiltration in glioblastoma
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/8aef5234162f41c9be3e1d253db29419
work_keys_str_mv	AT kiritsingh enhancingtcellchemotaxisandinfiltrationinglioblastoma AT kellymhotchkiss enhancingtcellchemotaxisandinfiltrationinglioblastoma AT kishakpatel enhancingtcellchemotaxisandinfiltrationinglioblastoma AT danielswilkinson enhancingtcellchemotaxisandinfiltrationinglioblastoma AT adityaamohan enhancingtcellchemotaxisandinfiltrationinglioblastoma AT sarahlcook enhancingtcellchemotaxisandinfiltrationinglioblastoma AT johnhsampson enhancingtcellchemotaxisandinfiltrationinglioblastoma
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Enhancing T Cell Chemotaxis and Infiltration in Glioblastoma

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