Lactic acidosis together with GM-CSF and M-CSF induces human macrophages toward an inflammatory pro-tumor phenotype - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Cancer Immunology Research Année : 2020

Lactic acidosis together with GM-CSF and M-CSF induces human macrophages toward an inflammatory pro-tumor phenotype

Clément Adam
  • Fonction : Auteur
  • PersonId : 1006995
Laurence Preisser
Pascale Pignon
Guillaume Tcherkez
Yves Delneste

Résumé

In established tumors, tumor-associated macrophages (TAMs) orchestrate non-resolving cancer-related inflammation and produce mediators favoring tumor growth, metastasis and angiogenesis. However, the factors conferring inflammatory and pro-tumor properties on human macrophages remain largely unknown. Most solid tumors have high lactate content. We therefore analyzed the impact of lactate on human monocyte differentiation. We report that prolonged lactic acidosis induces the differentiation of monocytes into macrophages with a phenotype including pro-tumor and inflammatory characteristics. These cells produce tumor growth factors, inflammatory cytokines and chemokines as well as low amounts of IL10. These effects of lactate require its metabolism and are associated with HIF-1α stabilization. The expression of some lactate-induced genes is dependent on autocrine M-CSF consumption. Finally, TAMs with pro-tumor and inflammatory characteristics (VEGFhigh CXCL8+ IL1β+) are found in solid ovarian tumors. These results show that tumor-derived lactate links the pro-tumor features of TAMs with their inflammatory properties. Treatments that reduce tumor glycolysis or tumor-associated acidosis may help combat cancer.

Domaines

Immunologie Cancer
Fichier principal
Vignette du fichier
Paolini et al-2020-Lactic acidosis together with GM-CSF and M-CSF.pdf (5.05 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)
Loading...

Dates et versions

hal-02442525 , version 1 (17-02-2020)

Identifiants

Citer

Léa Paolini, Clément Adam, Céline Beauvillain, Laurence Preisser, Simon Blanchard, et al.. Lactic acidosis together with GM-CSF and M-CSF induces human macrophages toward an inflammatory pro-tumor phenotype. Cancer Immunology Research, 2020, 8 (3), pp.383-395. ⟨10.1158/2326-6066.CIR-18-0749⟩. ⟨hal-02442525⟩
371 Consultations
496 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More