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...

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Bibliographic Details
Published in:Cancers 2021-10, Vol.13 (21), p.5367
Main Authors: Singh, Kirit, Hotchkiss, Kelly M, Patel, Kisha K, Wilkinson, Daniel S, Mohan, Aditya A, Cook, Sarah L, Sampson, John H
Format: Article
Language:English
Subjects:
Antigen-presenting cells
Antigens
Blood-brain barrier
Brain tumors
Cancer
Central nervous system
Chemokines
Chemotaxis
Cytotoxicity
Effector cells
Endothelium
Glioblastoma
Immunotherapy
Integrins
Lymphocytes
Lymphocytes T
Membrane proteins
Metastases
Parenchyma
Phenotypes
Review
Tumor cells
Tumor microenvironment
Tumor-infiltrating lymphocytes
Tumors
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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13215367