Abstract
Dendritic cells (DCs) are a heterogeneous group of antigen-presenting innate immune cells that regulate adaptive immunity, including against cancer. Therefore, understanding the precise activities of DCs in tumours and patients with cancer is important. The classification of DC subsets has historically been based on ontogeny; however, single-cell analyses are now additionally revealing a diversity of functional states of DCs in cancer. DCs can promote the activation of potent antitumour T cells and immune responses via numerous mechanisms, although they can also be hijacked by tumour-mediated factors to contribute to immune tolerance and cancer progression. Consequently, DC activities are often key determinants of the efficacy of immunotherapies, including immune-checkpoint inhibitors. Potentiating the antitumour functions of DCs or using them as tools to orchestrate short-term and long-term anticancer immunity has immense but as-yet underexploited therapeutic potential. In this Review, we outline the nature and emerging complexity of DC states as well as their functions in regulating adaptive immunity across different cancer types. We also describe how DCs are required for the success of current immunotherapies and explore the inherent potential of targeting DCs for cancer therapy. We focus on novel insights on DCs derived from patients with different cancers, single-cell studies of DCs and their relevance to therapeutic strategies.
Key points
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Dendritic cells (DCs) can induce adaptive anticancer immunity mainly via uptake and presentation of tumour-associated antigens, migration to lymph nodes and T cell priming, and recruitment and activation of tumour-infiltrating T cells.
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Intratumoural DCs originate from distinct ontogenic lineages and adopt heterogeneous functional states.
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The diversity of intratumoural DCs is generally conserved across species and cancer types; however, cancer-type-specific features of DCs in the blood, lymph nodes and tumours of patients are emerging.
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The efficacy of many immune-checkpoint inhibitors in patients with cancer is dependent on the anticancer functions of DCs, either directly or indirectly.
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The development of improved DC-based anticancer treatments, including agents targeting DCs in vivo and natural DC-based vaccines produced ex vivo, has the potential to improve patient outcomes and such treatments are generally safe.
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Combining DC-based anticancer treatments with other (immuno)therapies has shown promise in preclinical studies; however, patient selection, treatment sequencing and immunomonitoring require optimization in clinical studies to identify the most synergistic combinations.
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Acknowledgements
The authors acknowledge support from the “La Caixa” Foundation (ID 100010434) Junior Leader Fellowship LCF/BQ/PR20/11770008 to S.K.W. and INPhINIT Fellowship LCF/BQ/IN17/11620074 to I.H.-M. I.A.-B. and M.G. are recipients of a Becas de Formación del Profesorado Universitario (FPU) fellowship (FPU18/05752 and FPU20/01418, respectively) from the Spanish Ministry of Science. The Institute for Research in Biomedicine (IRB Barcelona) is supported by the CERCA Programme (Government of Catalonia) and by a Severo Ochoa Award of Excellence from the Ministry of Economy and Competitiveness (Government of Spain). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MICINN), and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (CEX2020-001041-S funded by MCIN/AEI/10.13039/501100011033).
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I.H.M. serves as a scientific adviser for Pulmobiotics. S.K.W. serves as a scientific adviser for ONA therapeutics. D.S. serves as a scientific adviser for Pulmobiotics and has research collaboration agreements with Inmunotek and Adendra Therapeutics. The other authors declare no competing interests.
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Heras-Murillo, I., Adán-Barrientos, I., Galán, M. et al. Dendritic cells as orchestrators of anticancer immunity and immunotherapy. Nat Rev Clin Oncol 21, 257–277 (2024). https://doi.org/10.1038/s41571-024-00859-1
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DOI: https://doi.org/10.1038/s41571-024-00859-1
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