Cargando…
Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression
The acidic tumor microenvironment in melanoma drives immune evasion by up-regulating cyclic adenosine monophosphate (cAMP) in tumor-infiltrating monocytes. Here we show that the release of non-toxic concentrations of an adenylate cyclase (AC) inhibitor from poly(sarcosine)-block-poly(L-glutamic acid...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514514/ https://www.ncbi.nlm.nih.gov/pubmed/34645812 http://dx.doi.org/10.1038/s41467-021-26269-w |
_version_ | 1784583407284518912 |
---|---|
author | Johann, Kerstin Bohn, Toszka Shahneh, Fatemeh Luther, Natascha Birke, Alexander Jaurich, Henriette Helm, Mark Klein, Matthias Raker, Verena K. Bopp, Tobias Barz, Matthias Becker, Christian |
author_facet | Johann, Kerstin Bohn, Toszka Shahneh, Fatemeh Luther, Natascha Birke, Alexander Jaurich, Henriette Helm, Mark Klein, Matthias Raker, Verena K. Bopp, Tobias Barz, Matthias Becker, Christian |
author_sort | Johann, Kerstin |
collection | PubMed |
description | The acidic tumor microenvironment in melanoma drives immune evasion by up-regulating cyclic adenosine monophosphate (cAMP) in tumor-infiltrating monocytes. Here we show that the release of non-toxic concentrations of an adenylate cyclase (AC) inhibitor from poly(sarcosine)-block-poly(L-glutamic acid γ-benzyl ester) (polypept(o)id) copolymer micelles restores antitumor immunity. In combination with selective, non-therapeutic regulatory T cell depletion, AC inhibitor micelles achieve a complete remission of established B16-F10-OVA tumors. Single-cell sequencing of melanoma-infiltrating immune cells shows that AC inhibitor micelles reduce the number of anti-inflammatory myeloid cells and checkpoint receptor expression on T cells. AC inhibitor micelles thus represent an immunotherapeutic measure to counteract melanoma immune escape. |
format | Online Article Text |
id | pubmed-8514514 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-85145142021-10-29 Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression Johann, Kerstin Bohn, Toszka Shahneh, Fatemeh Luther, Natascha Birke, Alexander Jaurich, Henriette Helm, Mark Klein, Matthias Raker, Verena K. Bopp, Tobias Barz, Matthias Becker, Christian Nat Commun Article The acidic tumor microenvironment in melanoma drives immune evasion by up-regulating cyclic adenosine monophosphate (cAMP) in tumor-infiltrating monocytes. Here we show that the release of non-toxic concentrations of an adenylate cyclase (AC) inhibitor from poly(sarcosine)-block-poly(L-glutamic acid γ-benzyl ester) (polypept(o)id) copolymer micelles restores antitumor immunity. In combination with selective, non-therapeutic regulatory T cell depletion, AC inhibitor micelles achieve a complete remission of established B16-F10-OVA tumors. Single-cell sequencing of melanoma-infiltrating immune cells shows that AC inhibitor micelles reduce the number of anti-inflammatory myeloid cells and checkpoint receptor expression on T cells. AC inhibitor micelles thus represent an immunotherapeutic measure to counteract melanoma immune escape. Nature Publishing Group UK 2021-10-13 /pmc/articles/PMC8514514/ /pubmed/34645812 http://dx.doi.org/10.1038/s41467-021-26269-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Johann, Kerstin Bohn, Toszka Shahneh, Fatemeh Luther, Natascha Birke, Alexander Jaurich, Henriette Helm, Mark Klein, Matthias Raker, Verena K. Bopp, Tobias Barz, Matthias Becker, Christian Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression |
title | Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression |
title_full | Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression |
title_fullStr | Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression |
title_full_unstemmed | Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression |
title_short | Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression |
title_sort | therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514514/ https://www.ncbi.nlm.nih.gov/pubmed/34645812 http://dx.doi.org/10.1038/s41467-021-26269-w |
work_keys_str_mv | AT johannkerstin therapeuticmelanomainhibitionbylocalmicellemediatedcyclicnucleotiderepression AT bohntoszka therapeuticmelanomainhibitionbylocalmicellemediatedcyclicnucleotiderepression AT shahnehfatemeh therapeuticmelanomainhibitionbylocalmicellemediatedcyclicnucleotiderepression AT luthernatascha therapeuticmelanomainhibitionbylocalmicellemediatedcyclicnucleotiderepression AT birkealexander therapeuticmelanomainhibitionbylocalmicellemediatedcyclicnucleotiderepression AT jaurichhenriette therapeuticmelanomainhibitionbylocalmicellemediatedcyclicnucleotiderepression AT helmmark therapeuticmelanomainhibitionbylocalmicellemediatedcyclicnucleotiderepression AT kleinmatthias therapeuticmelanomainhibitionbylocalmicellemediatedcyclicnucleotiderepression AT rakerverenak therapeuticmelanomainhibitionbylocalmicellemediatedcyclicnucleotiderepression AT bopptobias therapeuticmelanomainhibitionbylocalmicellemediatedcyclicnucleotiderepression AT barzmatthias therapeuticmelanomainhibitionbylocalmicellemediatedcyclicnucleotiderepression AT beckerchristian therapeuticmelanomainhibitionbylocalmicellemediatedcyclicnucleotiderepression |