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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-09-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fonc.2018.00414/full |
| _version_ | 1818382671294758912 |
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| author | Suneel D. Kamath Suneel D. Kamath Priya U. Kumthekar Priya U. Kumthekar |
| author_facet | Suneel D. Kamath Suneel D. Kamath Priya U. Kumthekar Priya U. Kumthekar |
| author_sort | Suneel D. Kamath |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T02:54:10Z |
| format | Article |
| id | doaj.art-e66513c49e7f428aa431e0eebe5f1e6c |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-14T02:54:10Z |
| publishDate | 2018-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-e66513c49e7f428aa431e0eebe5f1e6c2022-12-21T23:19:40ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2018-09-01810.3389/fonc.2018.00414416893Immune Checkpoint Inhibitors for the Treatment of Central Nervous System (CNS) Metastatic DiseaseSuneel D. Kamath0Suneel D. Kamath1Priya U. Kumthekar2Priya U. Kumthekar3Northwestern Medicine, Chicago, IL, United StatesFeinberg School of Medicine, Northwestern University, Chicago, IL, United StatesFeinberg School of Medicine, Northwestern University, Chicago, IL, United StatesRobert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, United StatesWhile 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.https://www.frontiersin.org/article/10.3389/fonc.2018.00414/fullimmunotherapybrain metastasisCNS metastasischeckpoint inhibitorsPD-1pembrolizumab |
| spellingShingle | Suneel D. Kamath Suneel D. Kamath Priya U. Kumthekar Priya U. Kumthekar Immune Checkpoint Inhibitors for the Treatment of Central Nervous System (CNS) Metastatic Disease Frontiers in Oncology immunotherapy brain metastasis CNS metastasis checkpoint inhibitors PD-1 pembrolizumab |
| 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 | immunotherapy brain metastasis CNS metastasis checkpoint inhibitors PD-1 pembrolizumab |
| url | https://www.frontiersin.org/article/10.3389/fonc.2018.00414/full |
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