Owing to their central role in the initiation and regulation of antitumor immunity, dendritic cells (DCs) have been widely tested for use in cancer immunotherapy. Despite several encouraging clinical applications, existing DC-based immunotherapy efforts have yielded inconsistent results. Recent work has identified strategies that may allow for more potent DC-based vaccines, such as the combination with antitumor agents that have the potential to synergistically enhance DC functions. Selected cytotoxic agents may stimulate DCs either by directly promoting their maturation or through the induction of immunogenic tumor cell death. Moreover, they may support DC-induced adaptive immune responses by disrupting tumor-induced immunosuppressive mechanisms via selective depletion or inhibition of regulatory subsets, such as myeloid-derived suppressor cells and/or regulatory T cells (Tregs). Here, we summarize our current knowledge on the capacity of anticancer chemotherapeutics to modulate DC phenotype and functions and the results of ongoing clinical trials evaluating the use of DC-based immunotherapy in combination with chemotherapy in cancer patients.
- MeSH
- antitumorózní látky terapeutické užití MeSH
- dendritické buňky imunologie MeSH
- imunoterapie MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- protinádorové vakcíny imunologie MeSH
- vakcinace * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
AIMS/HYPOTHESIS: Calorie restriction is an essential component in the treatment of obesity and associated diseases. Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) act as natural hypolipidaemics, reduce the risk of cardiovascular disease and could prevent the development of obesity and insulin resistance. We aimed to characterise the effectiveness and underlying mechanisms of the combination treatment with LC n-3 PUFA and 10% calorie restriction in the prevention of obesity and associated disorders in mice. METHODS: Male mice (C57BL/6J) were habituated to a corn-oil-based high-fat diet (cHF) for 2 weeks and then randomly assigned to various dietary treatments for 5 weeks or 15 weeks: (1) cHF, ad libitum; (2) cHF with LC n-3 PUFA concentrate replacing 15% (wt/wt) of dietary lipids (cHF + F), ad libitum; (3) cHF with calorie restriction (CR; cHF + CR); and (4) cHF + F + CR. Mice fed a chow diet were also studied. RESULTS: We show that white adipose tissue plays an active role in the amelioration of obesity and the improvement of glucose homeostasis by combining LC n-3 PUFA intake and calorie restriction in cHF-fed mice. Specifically in the epididymal fat in the abdomen, but not in other fat depots, synergistic induction of mitochondrial oxidative capacity and lipid catabolism was observed, resulting in increased oxidation of metabolic fuels in the absence of mitochondrial uncoupling, while low-grade inflammation was suppressed, reflecting changes in tissue levels of anti-inflammatory lipid mediators, namely 15-deoxy-Δ(12,15)-prostaglandin J(2) and protectin D1. CONCLUSIONS/INTERPRETATION: White adipose tissue metabolism linked to its inflammatory status in obesity could be modulated by combination treatment using calorie restriction and dietary LC n-3 PUFA to improve therapeutic strategies for metabolic syndrome.
- MeSH
- bílá tuková tkáň účinky léků metabolismus MeSH
- dieta s vysokým obsahem tuků MeSH
- dietní tuky farmakologie MeSH
- energetický metabolismus účinky léků MeSH
- imunohistochemie MeSH
- kalorická restrikce MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- kyseliny dokosahexaenové metabolismus MeSH
- kyseliny mastné omega-3 farmakologie MeSH
- metabolismus lipidů účinky léků MeSH
- myši obézní MeSH
- myši MeSH
- prostaglandin D2 analogy a deriváty metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIMS/HYPOTHESIS: Diets rich in n-3 polyunsaturated fatty acids, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against insulin resistance and obesity in rodents and increase insulin sensitivity in healthy humans. We tested whether the anti-diabetic effects of EPA and DHA involve enhanced production of the endogenous insulin sensitiser, adiponectin. METHODS: We studied the effects, in an obesity-promoting high-fat diet, of partial replacement of vegetable oils by EPA/DHA concentrate (6% EPA, 51% DHA) over a 5-week period in adult male C57BL/6J mice that either had free access to food or had their food intake restricted by 30%. At the end of the treatment, systemic markers of lipid and glucose metabolism and full-length adiponectin and leptin were measured. Adiponectin (Adipoq) and leptin (Lep) gene expression in dorsolumbar and epididymal white adipose tissue (WAT) and isolated adipocytes was quantified and adipokine production from WAT explants evaluated. RESULTS: In mice with free access to food, plasma triacylglycerols, NEFA, and insulin levels were lower in the presence of EPA/DHA, while glucose and leptin levels were not significantly altered. Food restriction decreased plasma triacylglycerols, glucose, insulin and leptin, but not adiponectin. EPA/DHA increased plasma adiponectin levels, independent of food intake, reflecting the stimulation of Adipoq expression in adipocytes and the release of adiponectin from WAT, particularly from epididymal fat. Expression of Lep and the release of leptin from WAT, while being extremely sensitive to caloric restriction, was unaltered by EPA/DHA. CONCLUSIONS/INTERPRETATION: Intake of diets rich in EPA and DHA leads to elevated systemic concentrations of adiponectin, largely independent of food intake or adiposity and explain, to some extent, their anti-diabetic effects.
- MeSH
- adiponektin biosyntéza genetika krev MeSH
- aktivace enzymů MeSH
- dietní tuky aplikace a dávkování farmakologie MeSH
- financování organizované MeSH
- glukosa metabolismus MeSH
- inzulin fyziologie krev MeSH
- inzulinová rezistence MeSH
- kalorická restrikce MeSH
- kyselina eikosapentaenová aplikace a dávkování farmakologie MeSH
- kyseliny dokosahexaenové aplikace a dávkování farmakologie MeSH
- leptin analýza fyziologie genetika krev MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- obezita patofyziologie prevence a kontrola MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- přijímání potravy MeSH
- proteinkinasy metabolismus MeSH
- regulace genové exprese MeSH
- složení těla MeSH
- triglyceridy krev MeSH
- tuková tkáň chemie metabolismus MeSH
- tukové buňky chemie metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
