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      Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review

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          Abstract

          Immunotherapy is emerging as a promising avenue in oncology, gaining increasing importance and offering substantial advantages when compared to chemotherapy or radiotherapy. However, in the context of immunotherapy, there is the potential for the immune system to either support or hinder the administered treatment. This review encompasses recent and pivotal studies that assess the influence of dietary elements, including vitamins, fatty acids, nutrients, small dietary molecules, dietary patterns, and caloric restriction, on the ability to modulate immune responses. Furthermore, the article underscores how these dietary factors have the potential to modify and enhance the effectiveness of anticancer immunotherapy. It emphasizes the necessity for additional research to comprehend the underlying mechanisms for optimizing the efficacy of anticancer therapy and defining dietary strategies that may reduce cancer-related morbidity and mortality. Persistent investigation in this field holds significant promise for improving cancer treatment outcomes and maximizing the benefits of immunotherapy.

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          Most cited references170

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          Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

          An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab--which blocks cytotoxic T-lymphocyte-associated antigen 4 to potentiate an antitumor T-cell response--administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. A total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P=0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)
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            Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer

            First-line therapy for advanced non-small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Among patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone in a phase 2 trial.
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              Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors

              Immune checkpoint inhibitors (ICI) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizeable minority of cancer patients. Here, we show that primary resistance to ICI can be due to abnormal gut microbiome composition. Antibiotics (ATB) inhibited the clinical benefit of ICI in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICI (but not from non-responding patients) into germ-free or ATB-treated mice ameliorated the antitumor effects of PD-1 blockade. Metagenomics of patient stools at diagnosis revealed correlations between clinical responses to ICI and the relative abundance of Akkermansia muciniphila. Oral supplementation with A. muciniphila post-FMT with non-responder feces restored the efficacy of PD-1 blockade in an IL-12-dependent manner, by increasing the recruitment of CCR9+CXCR3+CD4+ T lymphocytes into tumor beds.
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                Author and article information

                Contributors
                tomasz.pienkowski@sd.umb.edu.pl
                Journal
                Cell Death Dis
                Cell Death Dis
                Cell Death & Disease
                Nature Publishing Group UK (London )
                2041-4889
                9 April 2024
                9 April 2024
                April 2024
                : 15
                : 4
                : 254
                Affiliations
                [1 ]GRID grid.460348.d, ISNI 0000 0001 2286 1336, Prof. Waclaw Dabrowski Institute of Agricultural and Food Biotechnology State Research Institute, ; Rakowiecka 36, 02-532 Warsaw, Poland
                [2 ]Clinical Research Center, Medical University of Bialystok, ( https://ror.org/00y4ya841) M. Skłodowskiej-Curie 24a, 15-276 Bialystok, Poland
                [3 ]Department of Chemistry, Biology and Biotechnology, Bialystok University of Technology, ( https://ror.org/02bzfsy61) Wiejska 45 E, 15-351 Bialystok, Poland
                [4 ]Faculty of Chemistry, Jagiellonian University, ( https://ror.org/03bqmcz70) Gronostajowa 2, 30-387 Krakow, Poland
                [5 ]Faculty of Biology, Department of Animal and Human Physiology, University of Gdansk, ( https://ror.org/011dv8m48) W. Stwosza 59, 80-308 Gdansk, Poland
                Author information
                http://orcid.org/0000-0002-3169-1233
                Article
                6641
                10.1038/s41419-024-06641-6
                11004013
                38594256
                f6c007d9-ce9d-4200-a911-2a1fb654ec18
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 23 November 2023
                : 26 March 2024
                : 3 April 2024
                Categories
                Review Article
                Custom metadata
                © Associazione Differenziamento e Morte Cellulare ADMC 2024

                Cell biology
                tumour immunology,immunotherapy
                Cell biology
                tumour immunology, immunotherapy

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