| First Author | Johann K | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 5981 |
| PubMed ID | 34645812 | Mgi Jnum | J:348445 |
| Mgi Id | MGI:6787596 | Doi | 10.1038/s41467-021-26269-w |
| Citation | Johann K, et al. (2021) Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression. Nat Commun 12(1):5981 |
| abstractText | 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 gamma-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. |
