Cargando…
Immune Checkpoint Inhibitors for the Treatment of Central Nervous System (CNS) Metastatic Disease
While the CNS has long been viewed as an immune-privileged environment, a paradigm shift in neuro-immunology has elevated the role of systemic immunotherapy for the treatment of metastatic disease. Increasing knowledge regarding the presence of a CNS lymphatic system and the physical and biochemical...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171475/ https://www.ncbi.nlm.nih.gov/pubmed/30319977 http://dx.doi.org/10.3389/fonc.2018.00414 |
_version_ | 1783360799076515840 |
---|---|
author | Kamath, Suneel D. Kumthekar, Priya U. |
author_facet | Kamath, Suneel D. Kumthekar, Priya U. |
author_sort | Kamath, Suneel D. |
collection | PubMed |
description | While the CNS has long been viewed as an immune-privileged environment, a paradigm shift in neuro-immunology has elevated the role of systemic immunotherapy for the treatment of metastatic disease. Increasing knowledge regarding the presence of a CNS lymphatic system and the physical and biochemical alteration of the blood brain barrier (BBB) by the tumor microenvironment suggests immune cell trafficking in and out of the CNS is possible. Emerging clinical data suggest immune checkpoint inhibitors (ICIs) can stimulate T cells peripherally to in turn have anti-tumor effects in the CNS. For example, anti-programmed cell death-1 (PD-1) monotherapy with pembrolizumab has shown intracranial response rates of 20–30% in patients with melanoma or non-small cell lung cancer (NSCLC) brain metastases. The combination of nivolumab and ipilimumab [anti-PD-1 and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)] showed an intracranial response rate of 55% in patients with melanoma brain metastases. More data are needed to confirm these response rates and to determine mechanisms of efficacy and resistance. While local therapies such as stereotactic radiosurgery (SRS), whole-brain radiation therapy (WBRT), and surgery remain current mainstays, ICIS offer potential decreased neurotoxicity. This review summarizes the biological rationale for systemic immunotherapy to treat CNS metastatic disease, existing clinical data on ICIs in this setting and ongoing clinical trials exploring areas of unmet need. |
format | Online Article Text |
id | pubmed-6171475 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-61714752018-10-12 Immune Checkpoint Inhibitors for the Treatment of Central Nervous System (CNS) Metastatic Disease Kamath, Suneel D. Kumthekar, Priya U. Front Oncol Oncology While the CNS has long been viewed as an immune-privileged environment, a paradigm shift in neuro-immunology has elevated the role of systemic immunotherapy for the treatment of metastatic disease. Increasing knowledge regarding the presence of a CNS lymphatic system and the physical and biochemical alteration of the blood brain barrier (BBB) by the tumor microenvironment suggests immune cell trafficking in and out of the CNS is possible. Emerging clinical data suggest immune checkpoint inhibitors (ICIs) can stimulate T cells peripherally to in turn have anti-tumor effects in the CNS. For example, anti-programmed cell death-1 (PD-1) monotherapy with pembrolizumab has shown intracranial response rates of 20–30% in patients with melanoma or non-small cell lung cancer (NSCLC) brain metastases. The combination of nivolumab and ipilimumab [anti-PD-1 and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)] showed an intracranial response rate of 55% in patients with melanoma brain metastases. More data are needed to confirm these response rates and to determine mechanisms of efficacy and resistance. While local therapies such as stereotactic radiosurgery (SRS), whole-brain radiation therapy (WBRT), and surgery remain current mainstays, ICIS offer potential decreased neurotoxicity. This review summarizes the biological rationale for systemic immunotherapy to treat CNS metastatic disease, existing clinical data on ICIs in this setting and ongoing clinical trials exploring areas of unmet need. Frontiers Media S.A. 2018-09-27 /pmc/articles/PMC6171475/ /pubmed/30319977 http://dx.doi.org/10.3389/fonc.2018.00414 Text en Copyright © 2018 Kamath and Kumthekar. http://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 | Oncology Kamath, Suneel D. Kumthekar, Priya U. Immune Checkpoint Inhibitors for the Treatment of Central Nervous System (CNS) Metastatic Disease |
title | Immune Checkpoint Inhibitors for the Treatment of Central Nervous System (CNS) Metastatic Disease |
title_full | Immune Checkpoint Inhibitors for the Treatment of Central Nervous System (CNS) Metastatic Disease |
title_fullStr | Immune Checkpoint Inhibitors for the Treatment of Central Nervous System (CNS) Metastatic Disease |
title_full_unstemmed | Immune Checkpoint Inhibitors for the Treatment of Central Nervous System (CNS) Metastatic Disease |
title_short | Immune Checkpoint Inhibitors for the Treatment of Central Nervous System (CNS) Metastatic Disease |
title_sort | immune checkpoint inhibitors for the treatment of central nervous system (cns) metastatic disease |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171475/ https://www.ncbi.nlm.nih.gov/pubmed/30319977 http://dx.doi.org/10.3389/fonc.2018.00414 |
work_keys_str_mv | AT kamathsuneeld immunecheckpointinhibitorsforthetreatmentofcentralnervoussystemcnsmetastaticdisease AT kumthekarpriyau immunecheckpointinhibitorsforthetreatmentofcentralnervoussystemcnsmetastaticdisease |