Immunotherapy in CNS Cancers: the Role of Immune Cell Trafficking

Immunotherapy in CNS Cancers: the Role of Immune Cell Trafficking Abstract Glioblastoma (GBM) is a highly malignant CNS tumor with very poor survival despite intervention with conventional therapeutic strategies. Although the CNS is separated from the immune system by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), emerging evidence of immune surveillance and the selective infiltration of GBMs by immune suppressive cells indicates that there is breakdown or compromise of these physical barriers. This in turn offers hope that immunotherapy can be applied to specifically target and reduce tumor burden. One of the major setbacks in translating immunotherapy strategies is the hostile microenvironment of the tumor that inhibits trafficking of effector immune cells such as cytotoxic T lymphocytes into the CNS. Incorporating important findings from autoimmune disorders such as multiple sclerosis to understand and thereby enhance cytotoxic lymphocyte infiltration into GBM could augment immunotherapy strategies to treat this disease. However, although these therapies are designed to evoke a potent immune response, limited space in the brain and cranial vault reduces tolerance for immune therapy induced inflammation and resultant brain edema. Therefore, successful immunotherapy requires that a delicate balance be maintained between activating and retaining lasting anti-tumor immunity. Glioblastoma, Immunotherapy, lymphocyte migration, tumor micro-environment, blood-brain barrier Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuro-Oncology Oxford University Press

Immunotherapy in CNS Cancers: the Role of Immune Cell Trafficking

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Publisher
Oxford University Press
Copyright
Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2018.
ISSN
1522-8517
eISSN
1523-5866
D.O.I.
10.1093/neuonc/noy084
Publisher site
See Article on Publisher Site

Abstract

Abstract Glioblastoma (GBM) is a highly malignant CNS tumor with very poor survival despite intervention with conventional therapeutic strategies. Although the CNS is separated from the immune system by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), emerging evidence of immune surveillance and the selective infiltration of GBMs by immune suppressive cells indicates that there is breakdown or compromise of these physical barriers. This in turn offers hope that immunotherapy can be applied to specifically target and reduce tumor burden. One of the major setbacks in translating immunotherapy strategies is the hostile microenvironment of the tumor that inhibits trafficking of effector immune cells such as cytotoxic T lymphocytes into the CNS. Incorporating important findings from autoimmune disorders such as multiple sclerosis to understand and thereby enhance cytotoxic lymphocyte infiltration into GBM could augment immunotherapy strategies to treat this disease. However, although these therapies are designed to evoke a potent immune response, limited space in the brain and cranial vault reduces tolerance for immune therapy induced inflammation and resultant brain edema. Therefore, successful immunotherapy requires that a delicate balance be maintained between activating and retaining lasting anti-tumor immunity. Glioblastoma, Immunotherapy, lymphocyte migration, tumor micro-environment, blood-brain barrier Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2018. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Journal

Neuro-OncologyOxford University Press

Published: May 15, 2018

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