Dendritic Cells in Cancer Immunology and Immunotherapy

Dear Colleagues,

Dendritic cells (DCs) play a key role in pathogen sensing and antigen presentation, bridging innate and adaptive immunity. Two main phenotypically and functionally distinct DC subpopulations have been recognized: conventional DCs (cDCs), effective at antigen presentation and the activation of CD4+ and CD8+ T cells, and plasmacytoid DCs (pDCs), the principal type I interferon-producing cells. In the tumor microenvironment (TME), DCs can promote antitumor immunity and drive immune tolerance. DCs are central in processing and presenting tumor-associated antigens (TAA), thereby regulating T cell responses by cytokine production and co-stimulatory molecule expression. On the other hand, DCs can limit T cell effector activity by the engagement of inhibitory receptors. New types of DC subsets have recently been identified in human blood and tumor-draining lymph nodes by the single-cell RNA-sequencing approach, paving the way for a better understanding of DCs’ diversity and functions in cancer. Finally, the TME is enriched in immunosuppressive factors that can limit the recruitment and biological function of DCs.

Therapeutic targeting of these immunosuppressive mechanisms can boost antitumor immunity. Of relevance, immune checkpoint blockade (ICB) amplifies antitumor immune responses primed by DCs coupled with the accumulation of DCs within the TME. On the other hand, DC-mediated tolerance can be overcome by in vivo administration of neoantigens and adjuvants as well as TAA-loaded DCs or agonists of Toll-like receptors (TLR7/9); these approaches might positively synergize with and increase the efficacy of ICB regimens, and many clinical trials are ongoing (NCT03831295; NCT01983748; NCT02993315; NCT03747744; NCT01885702).

This Special Issue of Cancers, “Dendritic Cells in Cancer Immunology and Immunotherapy”, aims to shed light on the diversity of DC subsets in cancer and the potential impact of this heterogeneity on the current or new cancer therapies. We will welcome both original research articles and updated reviews on the biology and functions of human DC subsets in the tumor microenvironment and in cancer patients. Particularly, manuscripts dealing with the dual role of DCs to promote antitumor immunity or tolerance and its key implications for the efficacy of standard cancer therapies and immunotherapies as well as the development of optimal vaccination strategies, such as naturally occurring DC subsets or in vitro generated MoDCs targeting tumor neoantigens and combined with adjuvants, and the evaluation of TLR-7/9 agonist administration regimens, are welcome for submission. Manuscripts focusing on the involvement of the newly identified DC subtypes and their spatial distribution in cancer are also of great interest.

We look forward to receiving your contributions.

Prof. Dr. William Vermi
Dr. Matilde Monti
Guest Editors

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