Dendritic cells (DCs) are specialized antigen-presenting cells that are present at low abundance in the circulation and tissues; they serve as crucial immune sentinels by continually sampling their environment, migrating to secondary lymphoid organs and shaping adaptive immune responses through antigen presentation. Owing to their ability to orchestrate tolerogenic or immunogenic responses to a specific antigen, DCs have a pivotal role in antitumour immunity and the response to immune checkpoint blockade and other immunotherapeutic approaches. The multifaceted functions of DCs are acquired through a complex, multistage process called maturation. Although the role of inflammatory triggers in driving DC maturation was established decades ago, less is known about DC maturation in non-inflammatory contexts, such as during homeostasis and in cancer. The advent of single-cell technologies has enabled an unbiased, high-dimensional characterization of various DC states, including mature DCs. This approach has clarified the molecular programmes associated with DC maturation and also revealed how cancers exploit these pathways to subvert immune surveillance. In this Review, we discuss the mechanisms by which cancer disrupts DC maturation and highlight emerging therapeutic opportunities to modulate DC states. These insights could inform the development of DC-centric immunotherapies, expanding the arsenal of strategies to enhance antitumour immunity.
Author Info:
(1) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. The Tisch Cancer Institute, Icahn School of Medicine at
Mount Sinai, New York, NY, USA. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (2) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (3) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (4) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (5) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. (6) Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. miriam.merad@mssm.edu. The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. miriam.merad@mssm.edu. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. miriam.merad@mssm.edu. Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA. miriam.merad@mssm.edu.
Citation: Nat Rev Cancer 2025 Feb 7 Epub02/07/2025
