PT  - JOURNAL ARTICLE
AU  - Paolini, Léa
AU  - Adam, Clément
AU  - Beauvillain, Céline
AU  - Preisser, Laurence
AU  - Blanchard, Simon
AU  - Pignon, Pascale
AU  - Seegers, Valérie
AU  - Chevalier, Louise-Marie
AU  - Campone, Mario
AU  - Wernert, Romuald
AU  - Verrielle, Véronique
AU  - Raro, Pedro
AU  - Ifrah, Norbert
AU  - Lavoué, Vincent
AU  - Descamps, Philippe
AU  - Morel, Alain
AU  - Catros, Véronique
AU  - Tcherkez, Guillaume
AU  - Lenaers, Guy
AU  - Bocca, Cinzia
AU  - Kouassi Nzoughet, Judith
AU  - Procaccio, Vincent
AU  - Delneste, Yves
AU  - Jeannin, Pascale
TI  - Lactic Acidosis Together with GM-CSF and M-CSF Induces Human Macrophages toward an Inflammatory Protumor Phenotype
AID  - 10.1158/2326-6066.CIR-18-0749
DP  - 2020 Mar 01
TA  - Cancer Immunology Research
PG  - 383--395
VI  - 8
IP  - 3
4099  - http://cancerimmunolres.aacrjournals.org/content/8/3/383.short
4100  - http://cancerimmunolres.aacrjournals.org/content/8/3/383.full
SO  - Cancer Immunol Res2020 Mar 01; 8
AB  - In established tumors, tumor-associated macrophages (TAM) orchestrate nonresolving cancer-related inflammation and produce mediators favoring tumor growth, metastasis, and angiogenesis. However, the factors conferring inflammatory and protumor 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 protumor 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 hypoxia-inducible factor-1α stabilization. The expression of some lactate-induced genes is dependent on autocrine M-CSF consumption. Finally, TAMs with protumor and inflammatory characteristics (VEGFhigh CXCL8+ IL1β+) are found in solid ovarian tumors. These results show that tumor-derived lactate links the protumor features of TAMs with their inflammatory properties. Treatments that reduce tumor glycolysis or tumor-associated acidosis may help combat cancer.