Oleate but not stearate induces the regulatory phenotype of myeloid suppressor cells

Abstract Tumor infiltrating myeloid cells play contradictory roles in the tumor development. Dendritic cells and classical activated macrophages support anti-tumor immune activity via antigen presentation and induction of pro-inflammatory immune responses. Myeloid suppressor cells (MSCs), for instan...

Description complète

Enregistré dans:
Détails bibliographiques
Auteurs principaux: Hao Wu, Carl Weidinger, Franziska Schmidt, Jacqueline Keye, Marie Friedrich, Cansu Yerinde, Gerald Willimsky, Zhihai Qin, Britta Siegmund, Rainer Glauben
Format: article
Langue:EN
Publié: Nature Portfolio 2017
Sujets:
R
Q
Accès en ligne:https://doaj.org/article/8191c67f68f7481b88466fe86aaca7ae
Tags: Ajouter un tag
Pas de tags, Soyez le premier à ajouter un tag!
Description
Résumé:Abstract Tumor infiltrating myeloid cells play contradictory roles in the tumor development. Dendritic cells and classical activated macrophages support anti-tumor immune activity via antigen presentation and induction of pro-inflammatory immune responses. Myeloid suppressor cells (MSCs), for instance myeloid derived suppressor cells (MDSCs) or tumor associated macrophages play a critical role in tumor growth. Here, treatment with sodium oleate, an unsaturated fatty acid, induced a regulatory phenotype in the myeloid suppressor cell line MSC-2 and resulted in an increased suppression of activated T cells, paralleled by increased intracellular lipid droplets formation. Furthermore, sodium oleate potentiated nitric oxide (NO) production in MSC-2, thereby increasing their suppressive capacity. In primary polarized bone marrow cells, sodium oleate (C18:1) and linoleate (C18:2), but not stearate (C18:0) were identified as potent FFA to induce a regulatory phenotype. This effect was abrogated in MSC-2 as well as primary cells by specific inhibition of droplets formation while the inhibition of de novo FFA synthesis proved ineffective, suggesting a critical role for exogenous FFA in the functional induction of MSCs. Taken together our data introduce a new unsaturated fatty acid-dependent pathway shaping the functional phenotype of MSCs, facilitating the tumor escape from the immune system.