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Cancer immunotherapy via synergistic coactivation of myeloid receptors CD40 and Dectin-1.
- Source :
-
Science immunology [Sci Immunol] 2023 Nov 17; Vol. 8 (89), pp. eadj5097. Date of Electronic Publication: 2023 Nov 17. - Publication Year :
- 2023
-
Abstract
- Myeloid cells facilitate T cell immune evasion in cancer yet are pliable and have antitumor potential. Here, by cotargeting myeloid activation molecules, we leveraged the myeloid compartment as a therapeutic vulnerability in mouse models of pancreatic cancer. Myeloid cells in solid tumors expressed activation receptors including the pattern recognition receptor Dectin-1 and the TNF receptor superfamily member CD40. In mouse models of checkpoint inhibitor-resistant pancreatic cancer, coactivation of Dectin-1, via systemic β-glucan therapy, and CD40, with agonist antibody treatment, eradicated established tumors and induced immunological memory. Antitumor activity was dependent on cDC1s and T cells but did not require classical T cell-mediated cytotoxicity or blockade of checkpoint molecules. Rather, targeting CD40 drove T cell-mediated IFN-γ signaling, which converged with Dectin-1 activation to program distinct macrophage subsets to facilitate tumor responses. Thus, productive cancer immune surveillance in pancreatic tumors resistant to checkpoint inhibition can be invoked by coactivation of complementary myeloid signaling pathways.
- Subjects :
- Mice
Animals
CD40 Antigens
Immunotherapy
Pancreatic Neoplasms
Subjects
Details
- Language :
- English
- ISSN :
- 2470-9468
- Volume :
- 8
- Issue :
- 89
- Database :
- MEDLINE
- Journal :
- Science immunology
- Publication Type :
- Academic Journal
- Accession number :
- 37976347
- Full Text :
- https://doi.org/10.1126/sciimmunol.adj5097