MEK inhibition suppresses B regulatory cells and augments anti-tumor immunity.
Mitogen-activated protein kinase (MAPK) kinase (MEK) is an integral component of the RAS pathway and a therapeutic target in RAS-driven cancers. Although tumor responses to MEK inhibition are rarely durable, MEK inhibitors have shown substantial activity and durable tumor regressions when combined w...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0224600 |
| _version_ | 1811252148448526336 |
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| author | Mark Yarchoan Aditya A Mohan Lauren Dennison Teena Vithayathil Amanda Ruggieri Gregory B Lesinski Todd D Armstrong Nilofer S Azad Elizabeth M Jaffee |
| author_facet | Mark Yarchoan Aditya A Mohan Lauren Dennison Teena Vithayathil Amanda Ruggieri Gregory B Lesinski Todd D Armstrong Nilofer S Azad Elizabeth M Jaffee |
| author_sort | Mark Yarchoan |
| collection | DOAJ |
| description | Mitogen-activated protein kinase (MAPK) kinase (MEK) is an integral component of the RAS pathway and a therapeutic target in RAS-driven cancers. Although tumor responses to MEK inhibition are rarely durable, MEK inhibitors have shown substantial activity and durable tumor regressions when combined with systemic immunotherapies in preclinical models of RAS-driven tumors. MEK inhibitors have been shown to potentiate anti-tumor T cell immunity, but little is known about the effects of MEK inhibition on other immune subsets, including B cells. We show here that treatment with a MEK inhibitor reduces B regulatory cells (Bregs) in vitro, and reduces the number of Bregs in tumor draining lymph nodes in a colorectal cancer model in vivo. MEK inhibition does not impede anti-tumor humoral immunity, and B cells contribute meaningfully to anti-tumor immunity in the context of MEK inhibitor therapy. Treatment with a MEK inhibitor is associated with improved T cell infiltration and an enhanced response to anti-PD1 immunotherapy. Together these data indicate that MEK inhibition may reduce Bregs while sparing anti-tumor B cell function, resulting in enhanced anti-tumor immunity. |
| first_indexed | 2024-04-12T16:30:34Z |
| format | Article |
| id | doaj.art-deeb6c87dad04ce283915d1ea8fb3199 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T16:30:34Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-deeb6c87dad04ce283915d1ea8fb31992022-12-22T03:25:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-011410e022460010.1371/journal.pone.0224600MEK inhibition suppresses B regulatory cells and augments anti-tumor immunity.Mark YarchoanAditya A MohanLauren DennisonTeena VithayathilAmanda RuggieriGregory B LesinskiTodd D ArmstrongNilofer S AzadElizabeth M JaffeeMitogen-activated protein kinase (MAPK) kinase (MEK) is an integral component of the RAS pathway and a therapeutic target in RAS-driven cancers. Although tumor responses to MEK inhibition are rarely durable, MEK inhibitors have shown substantial activity and durable tumor regressions when combined with systemic immunotherapies in preclinical models of RAS-driven tumors. MEK inhibitors have been shown to potentiate anti-tumor T cell immunity, but little is known about the effects of MEK inhibition on other immune subsets, including B cells. We show here that treatment with a MEK inhibitor reduces B regulatory cells (Bregs) in vitro, and reduces the number of Bregs in tumor draining lymph nodes in a colorectal cancer model in vivo. MEK inhibition does not impede anti-tumor humoral immunity, and B cells contribute meaningfully to anti-tumor immunity in the context of MEK inhibitor therapy. Treatment with a MEK inhibitor is associated with improved T cell infiltration and an enhanced response to anti-PD1 immunotherapy. Together these data indicate that MEK inhibition may reduce Bregs while sparing anti-tumor B cell function, resulting in enhanced anti-tumor immunity.https://doi.org/10.1371/journal.pone.0224600 |
| spellingShingle | Mark Yarchoan Aditya A Mohan Lauren Dennison Teena Vithayathil Amanda Ruggieri Gregory B Lesinski Todd D Armstrong Nilofer S Azad Elizabeth M Jaffee MEK inhibition suppresses B regulatory cells and augments anti-tumor immunity. PLoS ONE |
| title | MEK inhibition suppresses B regulatory cells and augments anti-tumor immunity. |
| title_full | MEK inhibition suppresses B regulatory cells and augments anti-tumor immunity. |
| title_fullStr | MEK inhibition suppresses B regulatory cells and augments anti-tumor immunity. |
| title_full_unstemmed | MEK inhibition suppresses B regulatory cells and augments anti-tumor immunity. |
| title_short | MEK inhibition suppresses B regulatory cells and augments anti-tumor immunity. |
| title_sort | mek inhibition suppresses b regulatory cells and augments anti tumor immunity |
| url | https://doi.org/10.1371/journal.pone.0224600 |
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