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Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression
- Source :
- Nature Communications, Vol 12, Iss 1, Pp 1-9 (2021), Nature Communications, 12(1), Nature Communications
- Publication Year :
- 2021
- Publisher :
- Nature Portfolio, 2021.
-
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.<br />The acidic tumour microenvironment in melanoma drives immune evasion by cAMP in tumor-infiltrating monocytes. Here, the authors show that the release of an adenylate cyclase inhibitor from micelles restores antitumor immunity and, when combined with regulatory T cell depletion, leads to remission of established B16-F10-OVA tumors.
- Subjects :
- Skin Neoplasms
Receptor expression
Melanoma, Experimental
Gene Expression
General Physics and Astronomy
Injections, Intralesional
T-Lymphocytes, Regulatory
Mice
chemistry.chemical_compound
Cyclic AMP
Tumor Microenvironment
Myeloid Cells
Receptors, Immunologic
Melanoma
Micelles
Multidisciplinary
Chemistry
Esters
Tumor Burden
medicine.anatomical_structure
Polyglutamic Acid
Tumour immunology
Female
Adenylyl Cyclases
Regulatory T cell
Science
Antineoplastic Agents
Mice, Transgenic
chemical and pharmacologic phenomena
Cyclase
Article
General Biochemistry, Genetics and Molecular Biology
Cyclic nucleotide
Immune system
Benzyl Compounds
medicine
Animals
Humans
Cyclic adenosine monophosphate
Tumor microenvironment
Sarcosine
General Chemistry
medicine.disease
Immunity, Innate
Mice, Inbred C57BL
Interleukin 1 Receptor Antagonist Protein
Adenylyl Cyclase Inhibitors
Drug delivery
Cancer research
Tumor Escape
Peptides
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....a97cc8c5a7a8ef5f9b83b2a41ad1643a