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Bring on the brequinar: an approach to enforce the differentiation of myeloid-derived suppressor cells
Myeloid-derived suppressor cells (MDSCs) hinder antitumor immunity in multiple cancer types. While brequinar (BRQ), an inhibitor of dihydroorotate dehydrogenase, shows cytotoxicity in hematological malignancy, it has not yet been adapted to attenuate MDSCs by augmenting bone marrow progenitors in br...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9711868/ https://www.ncbi.nlm.nih.gov/pubmed/36453548 http://dx.doi.org/10.1172/JCI165506 |
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author | Horvat, Natalie K. Lesinski, Gregory B. |
author_facet | Horvat, Natalie K. Lesinski, Gregory B. |
author_sort | Horvat, Natalie K. |
collection | PubMed |
description | Myeloid-derived suppressor cells (MDSCs) hinder antitumor immunity in multiple cancer types. While brequinar (BRQ), an inhibitor of dihydroorotate dehydrogenase, shows cytotoxicity in hematological malignancy, it has not yet been adapted to attenuate MDSCs by augmenting bone marrow progenitors in breast cancer. In this issue of the JCI, Colligan et al. demonstrate that BRQ restored terminal differentiation of MDSCs. Using in vivo models of immunotherapy-resistant breast cancer, the authors uncovered a mechanism by which BRQ promoted myeloid cell differentiation by limiting their suppressive function and enhancing the efficacy of immune checkpoint blockade therapy. The findings offer insight into the biogenesis of MDSCs, provide an alternative avenue for cancers that remain unresponsive to conventional therapies, and may be extended to future translational studies in patients. |
format | Online Article Text |
id | pubmed-9711868 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-97118682022-12-05 Bring on the brequinar: an approach to enforce the differentiation of myeloid-derived suppressor cells Horvat, Natalie K. Lesinski, Gregory B. J Clin Invest Commentary Myeloid-derived suppressor cells (MDSCs) hinder antitumor immunity in multiple cancer types. While brequinar (BRQ), an inhibitor of dihydroorotate dehydrogenase, shows cytotoxicity in hematological malignancy, it has not yet been adapted to attenuate MDSCs by augmenting bone marrow progenitors in breast cancer. In this issue of the JCI, Colligan et al. demonstrate that BRQ restored terminal differentiation of MDSCs. Using in vivo models of immunotherapy-resistant breast cancer, the authors uncovered a mechanism by which BRQ promoted myeloid cell differentiation by limiting their suppressive function and enhancing the efficacy of immune checkpoint blockade therapy. The findings offer insight into the biogenesis of MDSCs, provide an alternative avenue for cancers that remain unresponsive to conventional therapies, and may be extended to future translational studies in patients. American Society for Clinical Investigation 2022-12-01 /pmc/articles/PMC9711868/ /pubmed/36453548 http://dx.doi.org/10.1172/JCI165506 Text en © 2022 Lesinski et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Commentary Horvat, Natalie K. Lesinski, Gregory B. Bring on the brequinar: an approach to enforce the differentiation of myeloid-derived suppressor cells |
title | Bring on the brequinar: an approach to enforce the differentiation of myeloid-derived suppressor cells |
title_full | Bring on the brequinar: an approach to enforce the differentiation of myeloid-derived suppressor cells |
title_fullStr | Bring on the brequinar: an approach to enforce the differentiation of myeloid-derived suppressor cells |
title_full_unstemmed | Bring on the brequinar: an approach to enforce the differentiation of myeloid-derived suppressor cells |
title_short | Bring on the brequinar: an approach to enforce the differentiation of myeloid-derived suppressor cells |
title_sort | bring on the brequinar: an approach to enforce the differentiation of myeloid-derived suppressor cells |
topic | Commentary |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9711868/ https://www.ncbi.nlm.nih.gov/pubmed/36453548 http://dx.doi.org/10.1172/JCI165506 |
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