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      Human dendritic cells in cancer

      Author(s): 1 , 2 , 3 , 4 , 5 , 6 , 7
      Publication date Created:
      Publication date (Print):
      Journal: Science Immunology
      Publisher: American Association for the Advancement of Science (AAAS)

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          Abstract

          Dendritic cells (DCs) are professional antigen-presenting cells, orchestrating innate and adaptive immunity during infections, autoimmune diseases, and malignancies. Since the discovery of DCs almost 50 years ago, our understanding of their biology in humans has increased substantially. Here, we review both antitumor and tolerogenic DC responses in cancer and discuss lineage-specific contributions by their functionally specialized subsets, including the conventional DC (cDC) subsets cDC1 and cDC2, the newly described DC3, and the plasmacytoid DCs (pDCs), focusing on the human setting. In addition, we review the lineage-unrestricted “mature DCs enriched in immunoregulatory molecules” (mregDC) state recently described across different human tumors.

          Abstract

          Recent advances on human dendritic cells have opened new avenues to address their subset-specific and cross-lineage programs in cancer.

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          Dendritic cells in cancer immunology and immunotherapy

          Stefanie Wculek, Francisco Cueto, Adriana Mujal … (2020)
          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.
          Article 0 comments Cited 880 times – based on 0 reviews     Review now
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            NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control

            Jan Böttcher, Eduardo Bonavita, Probir Chakravarty … (2018)
            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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              Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors

              Alexandra-Chloe Villani, Rahul Satija, Gary Reynolds … (2017)
              Dendritic cells (DCs) and monocytes play a central role in pathogen sensing, phagocytosis, and antigen presentation and consist of multiple specialized subtypes. However, their identities and interrelationships are not fully understood. Using unbiased single-cell RNA sequencing (RNA-seq) of ~2400 cells, we identified six human DCs and four monocyte subtypes in human blood. Our study reveals a new DC subset that shares properties with plasmacytoid DCs (pDCs) but potently activates T cells, thus redefining pDCs; a new subdivision within the CD1C+ subset of DCs; the relationship between blastic plasmacytoid DC neoplasia cells and healthy DCs; and circulating progenitor of conventional DCs (cDCs). Our revised taxonomy will enable more accurate functional and developmental analyses as well as immune monitoring in health and disease.
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                Author and article information

                Contributors
                Egle Kvedaraite: (View ORCID Profile)
                Florent Ginhoux: (View ORCID Profile)
                Journal
                Title: Science Immunology
                Abbreviated Title: Sci. Immunol.
                Publisher: American Association for the Advancement of Science (AAAS)
                ISSN (Electronic): 2470-9468
                Publication date Created: April 2022
                Publication date (Print): April 2022
                Volume: 7
                Issue: 70
                Affiliations
                [1 ]Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
                [2 ]Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
                [3 ]Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden.
                [4 ]Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), BIOPOLIS, Singapore, Singapore.
                [5 ]Inserm U1015, Gustave Roussy, Villejuif 94800, France.
                [6 ]Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, China.
                [7 ]Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore.
                Article
                DOI: 10.1126/sciimmunol.abm9409
                PubMed ID: 35363544
                SO-VID: e9d61d8e-d5f8-4e04-ac8c-8ccbabf553ad
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