Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Kerstin Johann
  • Toszka Bohn
  • Fatemeh Shahneh
  • Natascha Luther
  • Alexander Birke
  • Henriette Jaurich
  • Mark Helm
  • Matthias Klein
  • Verena K Raker
  • Tobias Bopp
  • Matthias Barz
  • Christian Becker
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000707028100035&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1038/s41467-021-26269-w
eISSN
2041-1723
Externe Identifier
  • Clarivate Analytics Document Solution ID: WG5IK
  • PubMed Identifier: 34645812
Ausgabe der Veröffentlichung
1
Zeitschrift
NATURE COMMUNICATIONS
Artikelnummer
ARTN 5981
Datum der Veröffentlichung
2021
Status
Published
Titel
Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression
Sub types
  • Article
Ausgabe der Zeitschrift
12

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Abstract
<jats:title>Abstract</jats:title><jats:p>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)-<jats:italic>block-</jats:italic>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.</jats:p>
Autoren
  • Kerstin Johann
  • Toszka Bohn
  • Fatemeh Shahneh
  • Natascha Luther
  • Alexander Birke
  • Henriette Jaurich
  • Mark Helm
  • Matthias Klein
  • Verena K Raker
  • Tobias Bopp
  • Matthias Barz
  • Christian Becker
DOI
10.1038/s41467-021-26269-w
eISSN
2041-1723
Ausgabe der Veröffentlichung
1
Zeitschrift
Nature Communications
Sprache
en
Artikelnummer
5981
Online publication date
2021
Status
Published online
Herausgeber
Springer Science and Business Media LLC
Herausgeber URL
http://dx.doi.org/10.1038/s41467-021-26269-w
Datum der Datenerfassung
2022
Titel
Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression
Ausgabe der Zeitschrift
12

Datenquelle: Crossref

Abstract
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.
Addresses
  • Institute of Organic Chemistry, Johannes Gutenberg University, Mainz, Germany.
Autoren
  • Kerstin Johann
  • Toszka Bohn
  • Fatemeh Shahneh
  • Natascha Luther
  • Alexander Birke
  • Henriette Jaurich
  • Mark Helm
  • Matthias Klein
  • Verena K Raker
  • Tobias Bopp
  • Matthias Barz
  • Christian Becker
DOI
10.1038/s41467-021-26269-w
eISSN
2041-1723
Externe Identifier
  • PubMed Identifier: 34645812
  • PubMed Central ID: PMC8514514
Funding acknowledgements
  • Deutsche Forschungsgemeinschaft: SFB 1066 A7
  • Deutsche Forschungsgemeinschaft: SFB 1066 B8
  • Deutsche Forschungsgemeinschaft: SFB 1066, B8
  • Deutsche Forschungsgemeinschaft: CRC 1292, 01
Open access
true
ISSN
2041-1723
Ausgabe der Veröffentlichung
1
Zeitschrift
Nature communications
Schlüsselwörter
  • Myeloid Cells
  • Animals
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Humans
  • Mice
  • Melanoma, Experimental
  • Skin Neoplasms
  • Esters
  • Benzyl Compounds
  • Polyglutamic Acid
  • Sarcosine
  • Peptides
  • Receptors, Immunologic
  • Cyclic AMP
  • Antineoplastic Agents
  • Tumor Burden
  • Injections, Intralesional
  • Tumor Escape
  • Gene Expression
  • Micelles
  • Female
  • T-Lymphocytes, Regulatory
  • Interleukin 1 Receptor Antagonist Protein
  • Immunity, Innate
  • Tumor Microenvironment
  • Adenylyl Cyclases
  • Adenylyl Cyclase Inhibitors
Sprache
eng
Medium
Electronic
Online publication date
2021
Open access status
Open Access
Paginierung
5981
Datum der Veröffentlichung
2021
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2021
Titel
Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression.
Sub types
  • Research Support, Non-U.S. Gov't
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
12

Files

https://www.nature.com/articles/s41467-021-26269-w.pdf https://europepmc.org/articles/PMC8514514?pdf=render

Datenquelle: Europe PubMed Central

Abstract
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.
Date of acceptance
2021
Autoren
  • Kerstin Johann
  • Toszka Bohn
  • Fatemeh Shahneh
  • Natascha Luther
  • Alexander Birke
  • Henriette Jaurich
  • Mark Helm
  • Matthias Klein
  • Verena K Raker
  • Tobias Bopp
  • Matthias Barz
  • Christian Becker
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/34645812
DOI
10.1038/s41467-021-26269-w
eISSN
2041-1723
Externe Identifier
  • PubMed Central ID: PMC8514514
Ausgabe der Veröffentlichung
1
Zeitschrift
Nat Commun
Schlüsselwörter
  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases
  • Animals
  • Antineoplastic Agents
  • Benzyl Compounds
  • Cyclic AMP
  • Esters
  • Female
  • Gene Expression
  • Humans
  • Immunity, Innate
  • Injections, Intralesional
  • Interleukin 1 Receptor Antagonist Protein
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Micelles
  • Myeloid Cells
  • Peptides
  • Polyglutamic Acid
  • Receptors, Immunologic
  • Sarcosine
  • Skin Neoplasms
  • T-Lymphocytes, Regulatory
  • Tumor Burden
  • Tumor Escape
  • Tumor Microenvironment
Sprache
eng
Country
England
Paginierung
5981
PII
10.1038/s41467-021-26269-w
Datum der Veröffentlichung
2021
Status
Published online
Datum, an dem der Datensatz öffentlich gemacht wurde
2021
Titel
Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
12

Datenquelle: PubMed

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