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      Trial watch: dietary interventions for cancer therapy

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          Dietary interventions have a profound impact on whole body metabolism, including oncometabolism (the metabolic features allowing cancer cells to proliferate) and immunometabolism (the catabolic and anabolic reactions that regulate immune responses). Recent preclinical studies demonstrated that multiple dietary changes can improve anticancer immunosurveillance of chemo-, radio- and immunotherapy. These findings have fostered the design of clinical trials evaluating the capacity of dietary interventions to synergize with treatment and hence limit tumor progression. Here, we discuss the scientific rationale for harnessing dietary interventions to improve the efficacy of anticancer therapy and present up-to-date information on clinical trials currently investigating this possibility.

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          Most cited references 92

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          The blockade of immune checkpoints in cancer immunotherapy.

          Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.
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            Sipuleucel-T immunotherapy for castration-resistant prostate cancer.

            Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer. In this double-blind, placebo-controlled, multicenter phase 3 trial, we randomly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T (341 patients) or placebo (171 patients) administered intravenously every 2 weeks, for a total of three infusions. The primary end point was overall survival, analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen (PSA) and lactate dehydrogenase. In the sipuleucel-T group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P=0.03). This reduction represented a 4.1-month improvement in median survival (25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group). The 36-month survival probability was 31.7% in the sipuleucel-T group versus 23.0% in the placebo group. The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test (hazard ratio, 0.77; 95% CI, 0.61 to 0.97; P=0.02) and after adjustment for use of docetaxel after the study therapy (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P=0.03). The time to objective disease progression was similar in the two study groups. Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills, fever, and headache. The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to disease progression was observed. (Funded by Dendreon; number, NCT00065442.)
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              Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants.

              Underweight and severe and morbid obesity are associated with highly elevated risks of adverse health outcomes. We estimated trends in mean body-mass index (BMI), which characterises its population distribution, and in the prevalences of a complete set of BMI categories for adults in all countries.

                Author and article information

                Taylor & Francis
                3 April 2019
                3 April 2019
                : 8
                : 7
                [a ]Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers , Paris, France
                [b ]INSERM, U1138 , Paris, France
                [c ]Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus , Villejuif, France
                [d ]Université Paris-Saclay , Orsay, France
                [e ]Fondation pour la Recherche Médicale , Paris, France
                [f ]Université Paris Descartes/Paris V, Sorbonne Paris Cité , Paris, France
                [g ]Université Pierre et Marie Curie/Paris VI , Paris, France
                [h ]INSERM U1015 , Villejuif, France
                [i ]CICBT507 , Villejuif, France
                [j ]Department of Radiation Oncology, Weill Cornell Medical College , New York, NY, USA
                [k ]Sandra and Edward Meyer Cancer Center , New York, NY, USA
                [l ]Department of Dermatology, Yale School of Medicine , New Haven, CT, USA
                [m ]Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP , Paris, France
                [n ]Department of Women’s and Children’s Health, Karolinska University Hospital , Stockholm, Sweden
                Author notes
                CONTACT Guido Kroemer kroemer@ ; Laurence Zitvogel laurence.zitvogel@ Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers , Paris, France
                © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.

                Tables: 1, References: 93, Pages: 8
                Funded by: Agence Nationale de la Recherche 10.13039/501100001665
                Award ID: E-Rare-2
                Funded by: Fondation pour la Recherche Médicale 10.13039/501100002915
                Award ID: FRM FDT201805005722
                Funded by: H2020 European Research Council 10.13039/100010663
                Award ID: Oncobiome
                This work was supported by the Agence Nationale de la Recherche [E-Rare-2]; Fondation pour la Recherche Médicale [FRM FDT201805005722]; H2020 European Union [Oncobiome].


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