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Tumor-associated human dendritic cell subsets: Phenotype, functional orientation, and clinical relevance

Journal

EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 52, Issue 11, Pages 1750-1758

Publisher

WILEY
DOI: 10.1002/eji.202149487

Keywords

Conventional dendritic cells; Monocyte-derived dendritic cells; Plasmacytoid dendritic cells; Tumor immunotherapy; Tumor microenvironment

Categories

Funding

  1. Elite Network of Bavaria International Junior Research Group Grant [N-LW-2016-370]
  2. German Research Foundation (DFG) [442405234, 424926990, 449174900, 461704785]
  3. TU Munich Junior Fellow Fund
  4. Projekt DEAL
  5. German Cancer aid (DKH) [70113847]

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Dendritic cells (DCs) are crucial in orchestrating anti-tumor immunity, capable of producing proinflammatory cytokines, initiating T-cell responses, and exhibiting direct cytotoxicity against tumor cells. The functionality of DCs depends on intrinsic properties and the tumor microenvironment, with immunogenic DCs promoting tumor elimination and tolerogenic DCs fostering tumor progression.
DCs play a pivotal role in orchestrating innate and adaptive antitumor immunity. Activated DCs can produce large amounts of various proinflammatory cytokines, initiate T-cell responses, and exhibit direct cytotoxicity against tumor cells. They also efficiently enhance the antitumoral properties of NK cells and T lymphocytes. Based on these capabilities, immunogenic DCs promote tumor elimination and are associated with improved survival of patients. Furthermore, they can essentially contribute to the clinical efficacy of immunotherapeutic strategies for cancer patients. However, depending on their intrinsic properties and the tumor microenvironment, DCs can be rendered dysfunctional and mediate tolerance by producing immunosuppressive cytokines and activating Treg cells. Such tolerogenic DCs can foster tumor progression and are linked to poor prognosis of patients. Here, we focus on recent studies exploring the phenotype, functional orientation, and clinical relevance of tumor-infiltrating conventional DC1, conventional DC2, plasmacytoid DCs, and monocyte-derived DCs in translational and clinical settings. In addition, recent findings demonstrating the influence of DCs on the efficacy of immunotherapeutic strategies are summarized.

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