AI Article Synopsis
- The acidic environment of melanoma tumors increases cAMP levels in immune cells, allowing the tumor to evade immune responses.
- Researchers delivered a safe adenylate cyclase inhibitor using specific micelles, which successfully enhanced the body’s antitumor immunity.
- The combination of the AC inhibitor with the removal of certain regulatory T cells led to the complete remission of tumors in a study model, suggesting a powerful new immunotherapy for melanoma.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514514 | PMC |
| http://dx.doi.org/10.1038/s41467-021-26269-w | DOI Listing |
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