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      Dendritic cell subsets in cancer immunity and tumor antigen sensing

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          Abstract

          Dendritic cells (DCs) exhibit a specialized antigen-presenting function and play crucial roles in both innate and adaptive immune responses. Due to their ability to cross-present tumor cell-associated antigens to naïve T cells, DCs are instrumental in the generation of specific T-cell-mediated antitumor effector responses in the control of tumor growth and tumor cell dissemination. Within an immunosuppressive tumor microenvironment, DC antitumor functions can, however, be severely impaired. In this review, we focus on the mechanisms of DC capture and activation by tumor cell antigens and the role of the tumor microenvironment in shaping DC functions, taking advantage of recent studies showing the phenotype acquisition, transcriptional state and functional programs revealed by scRNA-seq analysis. The therapeutic potential of DC-mediated tumor antigen sensing in priming antitumor immunity is also discussed.

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          The biology, function, and biomedical applications of exosomes

          The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.
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            Dendritic cells in cancer immunology and immunotherapy

            Dendritic cells (DCs) are a diverse group of specialized antigen-presenting cells with key roles in the initiation and regulation of innate and adaptive immune responses. As such, there is currently much interest in modulating DC function to improve cancer immunotherapy. Many strategies have been developed to target DCs in cancer, such as the administration of antigens with immunomodulators that mobilize and activate endogenous DCs, as well as the generation of DC-based vaccines. A better understanding of the diversity and functions of DC subsets and of how these are shaped by the tumour microenvironment could lead to improved therapies for cancer. Here we will outline how different DC subsets influence immunity and tolerance in cancer settings and discuss the implications for both established cancer treatments and novel immunotherapy strategies.
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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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                Author and article information

                Contributors
                silvano.sozzani@uniroma1.it
                Journal
                Cell Mol Immunol
                Cell Mol Immunol
                Cellular and Molecular Immunology
                Nature Publishing Group UK (London )
                1672-7681
                2042-0226
                22 March 2023
                22 March 2023
                May 2023
                : 20
                : 5
                : 432-447
                Affiliations
                [1 ]GRID grid.7637.5, ISNI 0000000417571846, Department of Molecular and Translational Medicine, , University of Brescia, ; Brescia, Italy
                [2 ]GRID grid.417728.f, ISNI 0000 0004 1756 8807, Humanitas Clinical and Research Center-IRCCS Rozzano, ; Milano, Italy
                [3 ]GRID grid.7841.a, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Molecular Medicine, , Sapienza University of Rome, ; Rome, Italy
                [4 ]GRID grid.419543.e, ISNI 0000 0004 1760 3561, IRCCS Neuromed, ; Pozzilli, IS Italy
                Author information
                http://orcid.org/0000-0002-3738-412X
                Article
                990
                10.1038/s41423-023-00990-6
                10203372
                36949244
                9a50d443-0f6a-4322-b311-047c3a1665c8
                © The Author(s) 2023

                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
                : 11 November 2022
                : 14 February 2023
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100005010, Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research);
                Award ID: IG-2017/20776
                Award ID: IG-2021/25680
                Award ID: 25307
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100003407, Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research);
                Award ID: 20177J4E75
                Award ID: 20178ALPCM_005
                Award Recipient :
                Funded by: Ministero dell'Istruzione, dell'Università e della Ricerca (Ministry of Education, University and Research)
                Categories
                Review Article
                Custom metadata
                © CSI and USTC 2023

                Immunology
                dendritic cell subsets,tumor microenvironment,migration,innate immune sensing,immune cell death,tumor-derived extracellular vesicles,dendritic cells,tumour immunology

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