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Journal article
Metabolic rewiring of macrophages by CpG potentiates clearance of cancer cells and overcomes tumor-expressed CD47-mediated 'don't-eat-me' signal
Nature immunology, v 20(3), pp 265-275
01 Mar 2019
PMID: 30664738
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 anti-tumor 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.
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Details
- Title
- Metabolic rewiring of macrophages by CpG potentiates clearance of cancer cells and overcomes tumor-expressed CD47-mediated 'don't-eat-me' signal
- Creators
- Mingen Liu - Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA.Roddy S. O'Connor - Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USASophie Trefely - Drexel UniversityKathleen Graham - Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA.Nathaniel W. Snyder - Drexel UniversityGregory L. Beatty - University of Pennsylvania
- Publication Details
- Nature immunology, v 20(3), pp 265-275
- Publisher
- Springer Nature
- Number of pages
- 13
- Grant note
- R01 CA197916; R03 HD092630; F30 CA196124 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA American Medical Association Foundation R01CA226983 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P30DK050306 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) K22ES026235 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) P30-DK050306 / Molecular Studies in Digestive and Liver Diseases grant from the National Institutes of Health R03HD092630 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000458893600012
- Scopus ID
- 2-s2.0-85060344636
- Other Identifier
- 991019168078004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Immunology