Summary Immune cells function in diverse metabolic environments. Tissues with low glucose and high lactate concentrations, such as the intestinal tract or ischemic tissues, frequently require immune responses to be more pro-tolerant avoiding unwanted reactions against self-antigens or commensal bacteria. T-regulatory cells (Treg) maintain peripheral tolerance, but how Treg function in low glucose lactate rich environments is unknown. We report that the Treg transcription factor Foxp3 reprograms T cell metabolism by suppressing Myc and glycolysis, enhancing oxidative phosphorylation, and increasing nicotinamide adenine dinucleotide oxidation. These adaptations allow Treg a metabolic advantage in low glucose, lactate rich environments; resisting lactate mediated suppression of T cell function and proliferation. This metabolic phenotype may explain how Tregs promote peripheral immune tolerance during tissue injury, but also how cancer cells evade immune destruction in the tumor microenvironment. Understanding Treg metabolism may therefore lead to novel approaches for selective immune modulation in cancer and autoimmune diseases.

Oral vancomycin treatment enhances the direct and abscopal antitumor effects of hypofractionated RT in preclinical melanoma and lung/cervical tumor models. Given the role of the gut microbiota in modulating immune cells that are also known to be involved in the response to RT, we examined whether the microbiota-regulated systemic immune response contributes to the RT-mediated anticancer immune response. The effects of oral vancomycin treatment are localized and impact the gut microbiota directly without any known systemic effects (21-23). Vancomycin (mostly targeting gram-positive bacteria) or a neomycin/metronidazole (Neo/Met) regimen (mostly targeting gram-negative bacteria

Lipid droplets (LD) are cytosolic inclusions present in most eukaryotic cells that contain a core rich in neutral lipids such as triacylglycerol (TAG) and cholesteryl esters (CE) and are surrounded by a phospholipid monolayer decorated with a variety of proteins, such as PAT family proteins (perilipin, adipose differentiation related protein, and tailinteracting protein of 47 kDa ) and caveolins (1-6). Initially regarded as inert neutral lipid-storage compartments, the interest for LD has increased recently because of their association with infl ammatory and metabolic disorders involving an excess lipid storage, including diabetes, obesity, and cardiovascular disease (7-10).LDs are generated by cells under different environmental conditions, suggesting a distinct pathophysiological signifi cance for each of these conditions. Cells generate lipid droplets from exogenous lipid sources, especially free fatty acids and cholesterol from serum lipoproteins (11-15), probably with an energy-storage purpose; however, when cells are under different stress signals, LD biogenesis occurs in the absence of external lipid via rearrangement of membrane phospholipids and fatty acids into newly formed TAG molecules (16,17).The leukocytes, cells typically associated with infl ammatory reactions can induce the rapid formation of LDs when exposed to proinfl ammatory stimuli (18-21). Moreover, it is becoming increasingly recognized that LDs are specialized intracellular sites for the biosynthesis and amplifi cation of the eicosanoid biosynthetic response during in fl ammation