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      Lipid droplets: platforms with multiple functions in cancer hallmarks

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          Abstract

          Lipid droplets (also known as lipid bodies) are lipid-rich, cytoplasmic organelles that play important roles in cell signaling, lipid metabolism, membrane trafficking, and the production of inflammatory mediators. Lipid droplet biogenesis is a regulated process, and accumulation of these organelles within leukocytes, epithelial cells, hepatocytes, and other nonadipocyte cells is a frequently observed phenotype in several physiologic or pathogenic situations and is thoroughly described during inflammatory conditions. Moreover, in recent years, several studies have described an increase in intracellular lipid accumulation in different neoplastic processes, although it is not clear whether lipid droplet accumulation is directly involved in the establishment of these different types of malignancies. This review discusses current evidence related to the biogenesis, composition and functions of lipid droplets related to the hallmarks of cancer: inflammation, cell metabolism, increased proliferation, escape from cell death, and hypoxia. Moreover, the potential of lipid droplets as markers of disease and targets for novel anti-inflammatory and antineoplastic therapies will be discussed.

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          NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control

          Summary Conventional type 1 dendritic cells (cDC1) are critical for antitumor immunity, and their abundance within tumors is associated with immune-mediated rejection and the success of immunotherapy. Here, we show that cDC1 accumulation in mouse tumors often depends on natural killer (NK) cells that produce the cDC1 chemoattractants CCL5 and XCL1. Similarly, in human cancers, intratumoral CCL5, XCL1, and XCL2 transcripts closely correlate with gene signatures of both NK cells and cDC1 and are associated with increased overall patient survival. Notably, tumor production of prostaglandin E2 (PGE2) leads to evasion of the NK cell-cDC1 axis in part by impairing NK cell viability and chemokine production, as well as by causing downregulation of chemokine receptor expression in cDC1. Our findings reveal a cellular and molecular checkpoint for intratumoral cDC1 recruitment that is targeted by tumor-derived PGE2 for immune evasion and that could be exploited for cancer therapy.
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            Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis.

            Tumor cells display progressive changes in metabolism that correlate with malignancy, including development of a lipogenic phenotype. How stored fats are liberated and remodeled to support cancer pathogenesis, however, remains unknown. Here, we show that the enzyme monoacylglycerol lipase (MAGL) is highly expressed in aggressive human cancer cells and primary tumors, where it regulates a fatty acid network enriched in oncogenic signaling lipids that promotes migration, invasion, survival, and in vivo tumor growth. Overexpression of MAGL in nonaggressive cancer cells recapitulates this fatty acid network and increases their pathogenicity-phenotypes that are reversed by an MAGL inhibitor. Impairments in MAGL-dependent tumor growth are rescued by a high-fat diet, indicating that exogenous sources of fatty acids can contribute to malignancy in cancers lacking MAGL activity. Together, these findings reveal how cancer cells can co-opt a lipolytic enzyme to translate their lipogenic state into an array of protumorigenic signals. PAPERFLICK:
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              Lipid accumulation and dendritic cell dysfunction in cancer

              Professional antigen presenting cells, dendritic cells (DC) are responsible for initiation and maintenance of immune responses. Here, we report that a substantial proportion of DCs in tumor-bearing mice and cancer patients have increased levels of triglycerides. Lipid accumulation in DCs was caused by increased uptake of extracellular lipids due to up-regulation of scavenger receptor A. DCs with high lipid content were not able to effectively stimulate allogeneic T cells or present tumor-associated antigens. DCs with high and normal lipid levels did not differ in expression of MHC and co-stimulatory molecules. However, lipid-laden DCs had reduced capacity to process antigens. Pharmacological normalization of lipid levels in DCs with an inhibitor of acetyl-CoA carboxylase restored the functional activity of DCs and substantially enhanced the effects of a cancer vaccine. These findings support the regulation of immune responses in cancer by manipulation of lipid levels in DCs.
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                Author and article information

                Contributors
                jpviola@inca.gov.br
                pbozza@ioc.fiocruz.br
                Journal
                Cell Death Dis
                Cell Death Dis
                Cell Death & Disease
                Nature Publishing Group UK (London )
                2041-4889
                6 February 2020
                6 February 2020
                February 2020
                : 11
                : 2
                : 105
                Affiliations
                [1 ]ISNI 0000 0001 0723 0931, GRID grid.418068.3, Laboratory of Immunopharmacology, Oswaldo Cruz Institute, FIOCRUZ, ; Rio de Janeiro, Brazil
                [2 ]ISNI 0000 0001 2294 473X, GRID grid.8536.8, Laboratory of Physiopathology, Polo Novo Cavaleiros, , Federal University of Rio De Janeiro (UFRJ), ; Macaé, Brazil
                [3 ]GRID grid.419166.d, Program of Immunology and Tumor Biology, Brazilian National Cancer Institute (INCA), ; Rio de Janeiro, Brazil
                Author information
                http://orcid.org/0000-0002-1360-6357
                http://orcid.org/0000-0002-1982-5841
                http://orcid.org/0000-0002-0698-3146
                http://orcid.org/0000-0001-8349-9529
                Article
                2297
                10.1038/s41419-020-2297-3
                7005265
                32029741
                4da65a52-80a4-43b0-937f-0e4e37cf4108
                © The Author(s) 2020

                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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 21 September 2019
                : 16 January 2020
                : 20 January 2020
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2020

                Cell biology
                lipids,cancer metabolism,inflammation
                Cell biology
                lipids, cancer metabolism, inflammation

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