Itaconic acid mediates crosstalk between macrophage metabolism and peritoneal tumors

@article{Weiss2018ItaconicAM,
  title={Itaconic acid mediates crosstalk between macrophage metabolism and peritoneal tumors},
  author={Jonathan M. Weiss and Luke C. Davies and Megan Karwan and Lilia V. Ileva and Michelle K Ozaki and Robert Y.S. Cheng and Lisa A. Ridnour and Christina M. Annunziata and David A Wink and Daniel W. McVicar},
  journal={The Journal of Clinical Investigation},
  year={2018},
  volume={128},
  pages={3794 - 3805}
}
Control of cellular metabolism is critical for efficient cell function, although little is known about the interplay between cell subset–specific metabolites in situ, especially in the tumor setting. Here, we determined how a macrophage-specific (Mϕ-specific) metabolite, itaconic acid, can regulate tumor progression in the peritoneum. We show that peritoneal tumors (B16 melanoma or ID8 ovarian carcinoma) elicited a fatty acid oxidation–mediated increase in oxidative phosphorylation (OXPHOS) and… 

Figures and Tables from this paper

Autophagic adaptation to oxidative stress alters peritoneal residential macrophage survival and ovarian cancer metastasis
TLDR
Human ovarian cancer–associated macrophages positive for complement receptor of the immunoglobulin superfamily (CRIg) were transcriptionally, metabolically, and functionally similar to murine Tim-4+ TAMs, and targeting CRIg+ (Tim-4+) TAMs may potentially treat patients with ovarian cancer with peritoneal metastasis.
Regulation of macrophage functions by FABP-mediated inflammatory and metabolic pathways.
Metabolism in tumor-associated macrophages
Itaconate: A Metabolite Regulates Inflammation Response and Oxidative Stress
TLDR
It is pointed out that itaconate is a novel and pivotal metabolic determinant of the immunoregulatory response in macrophages and studies that have improved the understanding of the connection between the immune response and metabolism are highlighted.
Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase
TLDR
It is demonstrated that nitric oxide produced by murine macrophages is responsible for TCA cycle alterations and citrate accumulation associated with polarization and that reprogramming of metabolism should be considered a result rather than a mediator of inflammatory polarization.
Understanding the Central Role of Citrate in the Metabolism of Cancer Cells and Tumors: An Update
TLDR
In preclinical cancer models, the administration of high doses of citrate showed various anti-cancer effects, such as the inhibition of glycolysis, the promotion of cytotoxic drugs sensibility and apoptosis, the neutralization of extracellular acidity, and the inhibited of tumors growth and of key signalling pathways.
Metabolic regulatory crosstalk between tumor microenvironment and tumor-associated macrophages
TLDR
The recent reports demonstrating the metabolic regulation between TME and TAMs are reviewed to seek the intrinsic mechanism of TAM phenotypic and functional changes through metabolic connections.
Itaconate: the poster child of metabolic reprogramming in macrophage function
TLDR
All of these studies point towards itaconate being a critical immunometabolite that could have far-reaching consequences for immunity, host defence and tumorigenesis.
Macrophage Origin, Metabolic Reprogramming and IL-1β Signaling: Promises and Pitfalls in Lung Cancer
TLDR
The current understanding of the bridge between TAM metabolism, IL-1β signaling, and effector functions in lung adenocarcinoma is reviewed and the challenges to successfully incorporating these pathways into current anticancer regimens are addressed.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 59 REFERENCES
Inhibition of Fatty Acid Oxidation Modulates Immunosuppressive Functions of Myeloid-Derived Suppressor Cells and Enhances Cancer Therapies
TLDR
Results support the possibility of testing FAO inhibition as a novel approach to block MDSC and enhance various cancer therapies and determine the energy metabolic pathway(s) used by M DSC.
Reshaping of Human Macrophage Polarization through Modulation of Glucose Catabolic Pathways
TLDR
The data indicate that GM-M Ø and M-MØ display distinct bioenergetic profiles, and that hypoxia triggers a transcriptomic switch in macrophages by promoting a HIF-1α/HIF-2α-dependent increase in ECAR.
Metabolic reprogramming in macrophages and dendritic cells in innate immunity
TLDR
New insights are providing a deeper understanding of the role of metabolic reprogramming in innate immunity, and another TCA cycle intermediate, succinate, activates HIF-1α and promotes inflammatory gene expression.
Peritoneal tissue-resident macrophages are metabolically poised to engage microbes using tissue-niche fuels
TLDR
It is proposed that tissue-resident macrophages are metabolically poised in situ to protect and exploit their tissue-niche by utilising locally available fuels to implement specific metabolic programmes upon microbial sensing.
Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression
Immunoresponsive Gene 1 and Itaconate Inhibit Succinate Dehydrogenase to Modulate Intracellular Succinate Levels*
TLDR
It is demonstrated that itaconate acts as an endogenous succinate dehydrogenase inhibitor to cause succinate accumulation and links the innate immune response and tricarboxylic acid metabolism to function of the electron transport chain.
Functional polarization of tumour-associated macrophages by tumour-derived lactic acid
TLDR
It is shown that lactic acid produced by tumour cells, as a by-product of aerobic or anaerobic glycolysis, has a critical function in signalling, through inducing the expression of vascular endothelial growth factor and the M2-like polarization of tumour-associated macrophages and this effect is mediated by hypoxia-inducible factor 1α (HIF1α).
Cell-intrinsic lysosomal lipolysis is essential for macrophage alternative activation
TLDR
It is found that the uptake of triacylglycerol substrates via the scavenger receptor CD36 and their subsequent lipolysis by lysosomal acid lipase (LAL) was important for the engagement of elevated oxidative phosphorylation, enhanced spare respiratory capacity (SRC), prolonged survival and expression of genes that together define M2 activation.
...
1
2
3
4
5
...