The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Metabolic rewiring of macrophages by CpG potentiates clearance of cancer cells and overcomes tumor-expressed CD47−mediated ‘don’t-eat-me’ signal
Open accessAbstract
Macrophages enforce antitumor immunity by engulfing and killing tumor cells. Although these functions are determined by a balance of stimulatory and inhibitory signals, the role of macrophage metabolism is unknown. Here, we study the capacity of macrophages to circumvent inhibitory activity mediated by CD47 on cancer cells. We show that stimulation with a CpG oligodeoxynucleotide, a Toll-like receptor 9 agonist, evokes changes in the central carbon metabolism of macrophages that enable antitumor activity, including engulfment of CD47+ cancer cells. CpG activation engenders a metabolic state that requires fatty acid oxidation and shunting of tricarboxylic acid cycle intermediates for de novo lipid biosynthesis. This integration of metabolic inputs is underpinned by carnitine palmitoyltransferase 1A and adenosine tri-phosphate citrate lyase, which, together, impart macrophages with antitumor potential capable of overcoming inhibitory CD47 on cancer cells. Our findings identify central carbon metabolism to be a novel determinant and potential therapeutic target for stimulating antitumor activity by macrophages. Macrophages have important antitumor functions but can be evaded by tumor-expressed CD47-dependent ‘don’t-eat-me’ signals. Beatty and colleagues demonstrate that the Toll-like receptor 9 ligand CpG metabolically reprograms macrophages to overcome don’t-eat-me signals.
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Metadata
- Authors
- Liu, M., O’Connor, R. S., Trefely, S., Graham, K., Snyder, N. W., & Beatty, G. L.
- Venue
- Nature Immunology
- Published
- 2019-01-21
- Volume
- 20
- Issue
- 3
- Pages
- 265-275
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2910735802
- Cited by
- 294
- References
- 11
- FWCI
- 9.93
- Type
- journal article
- Language
- en
- Open access
- green
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- Liu, M., O’Connor, R. S., Trefely, S., Graham, K., Snyder, N. W., & Beatty, G. L. (2019). Metabolic rewiring of macrophages by CpG potentiates clearance of cancer cells and overcomes tumor-expressed CD47−mediated ‘don’t-eat-me’ signal. Nature Immunology. https://doi.org/10.1038/s41590-018-0292-y
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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