Title
Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression
Author
Kerstin Johann, Toszka Bohn, Fatemeh Shahneh, Natascha Luther, Alexander Birke, Henriette Jaurich, Matthias Klein, Verena K. Raker, Tobias Bopp, Matthias Barz & Christian Becker
Year
2021
Journal
Nature Communications
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.
Full Article
Instrument
LC-2000, FT/IR-4100
Keywords
microenvironment, melanoma, cAMP,micelles, immunotherapeutics