Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression.

Autor: Johann K; Institute of Organic Chemistry, Johannes Gutenberg University, Mainz, Germany., Bohn T; Institute for Immunology, University Medical Center Mainz, Johannes Gutenberg University, Mainz, Germany., Shahneh F; Department of Dermatology, University Medical Center Mainz, Johannes Gutenberg University, Mainz, Germany., Luther N; Department of Dermatology, University Medical Center Mainz, Johannes Gutenberg University, Mainz, Germany., Birke A; Institute of Organic Chemistry, Johannes Gutenberg University, Mainz, Germany., Jaurich H; Institute of Organic Chemistry, Johannes Gutenberg University, Mainz, Germany.; Department of Dermatology, University Medical Center Mainz, Johannes Gutenberg University, Mainz, Germany., Helm M; Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany., Klein M; Institute for Immunology, University Medical Center Mainz, Johannes Gutenberg University, Mainz, Germany., Raker VK; Department of Dermatology, University Medical Center Mainz, Johannes Gutenberg University, Mainz, Germany.; Department of Dermatology, University Hospital Münster, Westfälische Wilhelms-University, Münster, Germany., Bopp T; Institute for Immunology, University Medical Center Mainz, Johannes Gutenberg University, Mainz, Germany. boppt@uni-mainz.de., Barz M; Institute of Organic Chemistry, Johannes Gutenberg University, Mainz, Germany. mbarz@lacdr.leidenuniv.nl.; Leiden Academic Center for Drug Research (LACDR), Leiden, Netherlands. mbarz@lacdr.leidenuniv.nl., Becker C; Department of Dermatology, University Medical Center Mainz, Johannes Gutenberg University, Mainz, Germany. christiangeorg.becker@ukmuenster.de.; Department of Dermatology, University Hospital Münster, Westfälische Wilhelms-University, Münster, Germany. christiangeorg.becker@ukmuenster.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Oct 13; Vol. 12 (1), pp. 5981. Date of Electronic Publication: 2021 Oct 13.
DOI: 10.1038/s41467-021-26269-w
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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