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Contrasting impact of corticosteroids on anti-PD-1 immunotherapy efficacy for tumor histologies located within or outside the central nervous system
Immune checkpoint blockade targeting programmed cell death protein 1 (PD-1) is emerging as an important treatment strategy in a growing list of cancers, yet its clinical benefits are limited to a subset of patients. Further investigation of tumor-intrinsic predictors of response and how extrinsic fa...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279341/ https://www.ncbi.nlm.nih.gov/pubmed/30524891 http://dx.doi.org/10.1080/2162402X.2018.1500108 |
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author | Maxwell, Russell Luksik, Andrew S. Garzon-Muvdi, Tomas Hung, Alice L. Kim, Eileen S. Wu, Adela Xia, Yuanxuan Belcaid, Zineb Gorelick, Noah Choi, John Theodros, Debebe Jackson, Christopher M. Mathios, Dimitrios Ye, Xiaobu Tran, Phuoc T. Redmond, Kristin J. Brem, Henry Pardoll, Drew M. Kleinberg, Lawrence R. Lim, Michael |
author_facet | Maxwell, Russell Luksik, Andrew S. Garzon-Muvdi, Tomas Hung, Alice L. Kim, Eileen S. Wu, Adela Xia, Yuanxuan Belcaid, Zineb Gorelick, Noah Choi, John Theodros, Debebe Jackson, Christopher M. Mathios, Dimitrios Ye, Xiaobu Tran, Phuoc T. Redmond, Kristin J. Brem, Henry Pardoll, Drew M. Kleinberg, Lawrence R. Lim, Michael |
author_sort | Maxwell, Russell |
collection | PubMed |
description | Immune checkpoint blockade targeting programmed cell death protein 1 (PD-1) is emerging as an important treatment strategy in a growing list of cancers, yet its clinical benefits are limited to a subset of patients. Further investigation of tumor-intrinsic predictors of response and how extrinsic factors, such as iatrogenic immunosuppression caused by conventional therapies, impact the efficacy of anti-PD-1 therapy are paramount. Given the widespread use of corticosteroids in cancer management and their immunosuppressive nature, this study sought to determine how corticosteroids influence anti-PD-1 responses and whether their effects were dependent on tumor location within the periphery versus central nervous system (CNS), which may have a more limiting immune environment. In well-established anti-PD-1-responsive murine tumor models, corticosteroid therapy resulted in systemic immune effects, including severe and persistent reductions in peripheral CD4+ and CD8 + T cells. Corticosteroid treatment was found to diminish the efficacy of anti-PD-1 therapy in mice bearing peripheral tumors with responses correlating with peripheral CD8/Treg ratio changes. In contrast, in mice bearing intracranial tumors, corticosteroids did not abrogate the benefits conferred by anti-PD-1 therapy. Despite systemic immune changes, anti-PD-1-mediated antitumor immune responses remained intact during corticosteroid treatment in mice bearing intracranial tumors. These findings suggest that anti-PD-1 responses may be differentially impacted by concomitant corticosteroid use depending on tumor location within or outside the CNS. As an immune-specialized site, the CNS may potentially play a protective role against the immunosuppressive effects of corticosteroids, thus sustaining antitumor immune responses mediated by PD-1 blockade. |
format | Online Article Text |
id | pubmed-6279341 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-62793412018-12-06 Contrasting impact of corticosteroids on anti-PD-1 immunotherapy efficacy for tumor histologies located within or outside the central nervous system Maxwell, Russell Luksik, Andrew S. Garzon-Muvdi, Tomas Hung, Alice L. Kim, Eileen S. Wu, Adela Xia, Yuanxuan Belcaid, Zineb Gorelick, Noah Choi, John Theodros, Debebe Jackson, Christopher M. Mathios, Dimitrios Ye, Xiaobu Tran, Phuoc T. Redmond, Kristin J. Brem, Henry Pardoll, Drew M. Kleinberg, Lawrence R. Lim, Michael Oncoimmunology Original Research Immune checkpoint blockade targeting programmed cell death protein 1 (PD-1) is emerging as an important treatment strategy in a growing list of cancers, yet its clinical benefits are limited to a subset of patients. Further investigation of tumor-intrinsic predictors of response and how extrinsic factors, such as iatrogenic immunosuppression caused by conventional therapies, impact the efficacy of anti-PD-1 therapy are paramount. Given the widespread use of corticosteroids in cancer management and their immunosuppressive nature, this study sought to determine how corticosteroids influence anti-PD-1 responses and whether their effects were dependent on tumor location within the periphery versus central nervous system (CNS), which may have a more limiting immune environment. In well-established anti-PD-1-responsive murine tumor models, corticosteroid therapy resulted in systemic immune effects, including severe and persistent reductions in peripheral CD4+ and CD8 + T cells. Corticosteroid treatment was found to diminish the efficacy of anti-PD-1 therapy in mice bearing peripheral tumors with responses correlating with peripheral CD8/Treg ratio changes. In contrast, in mice bearing intracranial tumors, corticosteroids did not abrogate the benefits conferred by anti-PD-1 therapy. Despite systemic immune changes, anti-PD-1-mediated antitumor immune responses remained intact during corticosteroid treatment in mice bearing intracranial tumors. These findings suggest that anti-PD-1 responses may be differentially impacted by concomitant corticosteroid use depending on tumor location within or outside the CNS. As an immune-specialized site, the CNS may potentially play a protective role against the immunosuppressive effects of corticosteroids, thus sustaining antitumor immune responses mediated by PD-1 blockade. Taylor & Francis 2018-09-06 /pmc/articles/PMC6279341/ /pubmed/30524891 http://dx.doi.org/10.1080/2162402X.2018.1500108 Text en © 2018 The Author(s). Published with license by Taylor & Francis Group, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
spellingShingle | Original Research Maxwell, Russell Luksik, Andrew S. Garzon-Muvdi, Tomas Hung, Alice L. Kim, Eileen S. Wu, Adela Xia, Yuanxuan Belcaid, Zineb Gorelick, Noah Choi, John Theodros, Debebe Jackson, Christopher M. Mathios, Dimitrios Ye, Xiaobu Tran, Phuoc T. Redmond, Kristin J. Brem, Henry Pardoll, Drew M. Kleinberg, Lawrence R. Lim, Michael Contrasting impact of corticosteroids on anti-PD-1 immunotherapy efficacy for tumor histologies located within or outside the central nervous system |
title | Contrasting impact of corticosteroids on anti-PD-1 immunotherapy efficacy for tumor histologies located within or outside the central nervous system |
title_full | Contrasting impact of corticosteroids on anti-PD-1 immunotherapy efficacy for tumor histologies located within or outside the central nervous system |
title_fullStr | Contrasting impact of corticosteroids on anti-PD-1 immunotherapy efficacy for tumor histologies located within or outside the central nervous system |
title_full_unstemmed | Contrasting impact of corticosteroids on anti-PD-1 immunotherapy efficacy for tumor histologies located within or outside the central nervous system |
title_short | Contrasting impact of corticosteroids on anti-PD-1 immunotherapy efficacy for tumor histologies located within or outside the central nervous system |
title_sort | contrasting impact of corticosteroids on anti-pd-1 immunotherapy efficacy for tumor histologies located within or outside the central nervous system |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279341/ https://www.ncbi.nlm.nih.gov/pubmed/30524891 http://dx.doi.org/10.1080/2162402X.2018.1500108 |
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