Dendritic cells initiate adaptive immune responses, leading either to control cancer by effector T cells or to exacerbate cancer by regulatory T cells that inhibit IFN-γ-mediated Th1-type response. Dendritic cells can also induce Th17-type immunity, mediated by IL-17A. However, the controversial role of this cytokine in cancer requires further investigations. We generated dendritic cells from peripheral blood monocytes to investigate lifespan, phenotype and chemoresistance of dendritic cells, treated with IL-17A with or without IFN-γ. Studying the expression of Bcl-2 family members, we demonstrated that dendritic cells constitutively express one pro-survival Bcl-2 member: MCL1. Immature dendritic cells were CD40lowHLADRlow CD1a+ MCL1+, did not express CD14, CD68 or BCL2A1, and displayed a short 2-day lifespan. IL-17A-treated DC exhibited a semi-mature (CD40high HLADRlow) pre-M2 (CCL22+ CD206+ CD163+ IL1RN+ IL-10− CXCL10− IL-12−) mixed (CD1a+ CD14+ CD68+) macrophage-dendritic cell phenotype. They efficiently exerted mannose receptor-mediated endocytosis and did not produce superoxide anions, in the absence of TLR engagement. Interestingly, IL-17A promoted a long-term survival of dendritic cells, beyond 12 days, that correlated to BCL2A1 induction, a pro-survival Bcl-2 family member. BCL2A1 transcription was activated by NF-κB, downstream of IL-17A transduction. Thus, immature dendritic cells only express MCL1, whereas IL-17A-treated dendritic cells concomitantly expressed two pro-survival Bcl-2 family members: MCL1 and BCL2A1. These latter developed chemoresistance to 11 of the 17 chemotherapy agents tested. However, high doses of either vinblastine or cytarabine decreased MCL1 expression and induced dendritic cell death. When IL-17A is produced in vivo, administration of anti-IL-17A biotherapy may impair dendritic cell survival by targeting BCL2A1 expression. Consequently, depending on the effector or regulatory role of dendritic cells, blocking IL-17A, may be either dangerous or beneficial for cancer outcomes, thus contributing to the apparent controversy around the role of IL-17A in cancer.

The emerging fi eld of research called immunometabolism results from mutual interactions between metabolism and immune system. Chronic infl ammation and changes in immune cells participate in metabolic disorders such as atherosclerosis, type 2 diabetes mellitus, and obesity ( 1 ), which are now consequently considered both metabolic and chronic infl ammatory diseases. Conversely, the physiopathological remodeling of cell-intrinsic metabolic pathways modulates the functions of immune cells ( 1, 2 ).Macrophages and dendritic cells (DCs) are antigenpresenting cells, distributed in the tissues as sentinels of the immune system. They play major roles in many pathological conditions, in line with their ability to produce cytokines and