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Myeloid-targeted immunotherapies act in synergy to induce inflammation and antitumor immunity
- Source :
- The Journal of Experimental Medicine; March 2018, Vol. 215 Issue: 3 p877-893, 17p
- Publication Year :
- 2018
-
Abstract
- Eliciting effective antitumor immune responses in patients who fail checkpoint inhibitor therapy is a critical challenge in cancer immunotherapy, and in such patients, tumor-associated myeloid cells and macrophages (TAMs) are promising therapeutic targets. We demonstrate in an autochthonous, poorly immunogenic mouse model of melanoma that combination therapy with an agonistic anti-CD40 mAb and CSF-1R inhibitor potently suppressed tumor growth. Microwell assays to measure multiplex protein secretion by single cells identified that untreated tumors have distinct TAM subpopulations secreting MMP9 or cosecreting CCL17/22, characteristic of an M2-like state. Combination therapy reduced the frequency of these subsets, while simultaneously inducing a separate polyfunctional inflammatory TAM subset cosecreting TNF-α, IL-6, and IL-12. Tumor suppression by this combined therapy was partially dependent on T cells, and on TNF-α and IFN-γ. Together, this study demonstrates the potential for targeting TAMs to convert a “cold” into an “inflamed” tumor microenvironment capable of eliciting protective T cell responses.
Details
- Language :
- English
- ISSN :
- 00221007 and 15409538
- Volume :
- 215
- Issue :
- 3
- Database :
- Supplemental Index
- Journal :
- The Journal of Experimental Medicine
- Publication Type :
- Periodical
- Accession number :
- ejs44954314
- Full Text :
- https://doi.org/10.1084/jem.20171435