Tumor-afgeleid lactaat reguleert TAM metabolism en functie

Xenia Geeraerts, Emile Clappaert, Dorien Broekaert, Sweta Parik, Yvon Elkrim, Damya Laoui, Jan Van Den Bossche, Sarah-Maria Fendt, Jo Van Ginderachter

Onderzoeksoutput: Poster

Samenvatting

One of the outstanding challenges in macrophage biology is to understand how particular microenvironmental cues translate into macrophage functions and ultimately in the outcome of macrophage-regulated pathophysiological processes. A very relevant disease in this respect is cancer. Tumor-associated macrophages (TAM) are amongst the most abundant inflammatory cells in tumors and a significant correlation was found between high TAM density and a worse prognosis for most cancers. The co-existence of distinct, specialized TAM subpopulations within the same tumor has been defined before and indicated the presence of protumoral M2-like MHC-II(lo) TAM and antitumoral M1-like MHC-II(hi) TAM. Therefore, strategies that reprogram protumoral M2 TAM into an antitumoral M1 phenotype, are currently highly investigated.

In this context, our work has focused on unravelling the largely unknown metabolic phenotype of TAM subsets in a murine lung carcinoma model. Interestingly, we found that the metabolic phenotype of MHC-II(hi) TAM and MHC-II(lo) TAM shows similarities with in vitro stimulated M1 and M2 macrophages, characterized by aerobic glycolysis followed by a truncated TCA cycle and oxidative metabolism, respectively. 13C tracer analysis revealed lactate, which is known to highly contribute to tumor acidosis, as a carbon source for MHC-II(lo) TAM which can be fueled into the TCA cycle coupled to OXPHOS. Our data suggest that lactate strongly affects macrophage metabolism, as MHC-II(hi) TAM metabolism is disturbed and forced towards an intact TCA cycle in the presence of lactate.

Overall, our findings suggest that lactate might be an important regulator of TAM metabolism. Since metabolism is shown to be inextricably connected to immune cell function, interfering with (lactate) metabolism could be an elegant way to metabolically repolarize TAM towards an antitumoral phenotype and subsequently affect tumor growth and metastasis.
Originele taal-2English
StatusPublished - 8 jun 2018
EvenementLKI-Oncoforum 2018 - Leuven, Belgium
Duur: 8 jun 2018 → …
https://www.uzleuven-kuleuven.be/lki/en/lki-oncoforum-2018

Conference

ConferenceLKI-Oncoforum 2018
LandBelgium
StadLeuven
Periode8/06/18 → …
Internet adres

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