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Cancers
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Dendritic Cells in Cancer Immunology and Immunotherapy
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Dendritic Cells in Cancer Immunology and Immunotherapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (15 March 2023) | Viewed by 11262

Special Issue Editors

Prof. Dr. William Vermi

E-Mail Website
Guest Editor
Section of Pathology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
Interests: cancer; tumor microenvironment; immunotherapy; immune escape mechanisms; human immunity; dendritic cells
Dr. Matilde Monti

E-Mail Website
Guest Editor
Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
Interests: melanoma; microenvironment; immunotherapy; immune escape mechanisms; plasmacytoid dendritic cells; Toll-like receptors; interferons

Special Issue Information

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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • dendritic cells
  • antigen presentation
  • antitumor immunity
  • immune tolerance
  • tumor microenvironment
  • tumor neoantigens
  • cancer immunotherapy
  • immune checkpoint blockade
  • DC vaccines
  • clinical trials

Published Papers (5 papers)

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Research

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20 pages, 3307 KiB  
Article
Plasmacytoid Dendritic Cell, Slan+-Monocyte and Natural Killer Cell Counts Function as Blood Cell-Based Biomarkers for Predicting Responses to Immune Checkpoint Inhibitor Monotherapy in Non-Small Cell Lung Cancer Patients
by Francesca Pettinella, Chiara Lattanzi, Marta Donini, Elena Caveggion, Olivia Marini, Giulia Iannoto, Sara Costa, Elena Zenaro, Tiago Moderno Fortunato, Sara Gasperini, Matteo Giani, Lorenzo Belluomini, Marco Sposito, Jessica Insolda, Ilaria Mariangela Scaglione, Michele Milella, Annalisa Adamo, Ornella Poffe, Vincenzo Bronte, Stefano Dusi, Marco A. Cassatella, Stefano Ugel, Sara Pilotto and Patrizia Scapiniadd Show full author list remove Hide full author list
Cancers 2023, 15(21), 5285; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15215285 - 03 Nov 2023
Cited by 1 | Viewed by 860
Abstract
The advent of immune checkpoint inhibitors (ICIs), for instance, programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) blockers, has greatly improved the outcome of patients affected by non-small cell lung cancer (NSCLC). However, most NSCLC patients either do not respond to ICI monotherapy [...] Read more.
The advent of immune checkpoint inhibitors (ICIs), for instance, programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) blockers, has greatly improved the outcome of patients affected by non-small cell lung cancer (NSCLC). However, most NSCLC patients either do not respond to ICI monotherapy or develop resistance to it after an initial response. Therefore, the identification of biomarkers for predicting the response of patients to ICI monotherapy represents an urgent issue. Great efforts are currently dedicated toward identifying blood-based biomarkers to predict responses to ICI monotherapy. In this study, more commonly utilized blood-based biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR) and the lung immune prognostic index (LIPI) score, as well as the frequency/number and activation status of various types of circulating innate immune cell populations, were evaluated in NSCLC patients at baseline before therapy initiation. The data indicated that, among all the parameters tested, low plasmacytoid dendritic cell (pDC), slan+-monocyte and natural killer cell counts, as well as a high LIPI score and elevated PD-L1 expression levels on type 1 conventional DCs (cDC1s), were independently correlated with a negative response to ICI therapy in NSCLC patients. The results from this study suggest that the evaluation of innate immune cell numbers and phenotypes may provide novel and promising predictive biomarkers for ICI monotherapy in NSCLC patients. Full article
(This article belongs to the Special Issue Dendritic Cells in Cancer Immunology and Immunotherapy)
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22 pages, 2677 KiB  
Article
Immuno-Contexture and Immune Checkpoint Molecule Expression in Mismatch Repair Proficient Colorectal Carcinoma
by Mauro Giacomelli, Matilde Monti, Diego Cesare Pezzola, Silvia Lonardi, Mattia Bugatti, Francesco Missale, Rossella Cioncada, Laura Melocchi, Viviana Giustini, Vincenzo Villanacci, Carla Baronchelli, Stefania Manenti, Luisa Imberti, Emanuele Giurisato and William Vermi
Cancers 2023, 15(12), 3097; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15123097 - 07 Jun 2023
Cited by 2 | Viewed by 1596
Abstract
Colorectal carcinoma (CRC) represents a lethal disease with heterogeneous outcomes. Only patients with mismatch repair (MMR) deficient CRC showing microsatellite instability and hyper-mutated tumors can obtain clinical benefits from current immune checkpoint blockades; on the other hand, immune- or target-based therapeutic strategies are [...] Read more.
Colorectal carcinoma (CRC) represents a lethal disease with heterogeneous outcomes. Only patients with mismatch repair (MMR) deficient CRC showing microsatellite instability and hyper-mutated tumors can obtain clinical benefits from current immune checkpoint blockades; on the other hand, immune- or target-based therapeutic strategies are very limited for subjects with mismatch repair proficient CRC (CRCpMMR). Here, we report a comprehensive typing of immune infiltrating cells in CRCpMMR. We also tested the expression and interferon-γ-modulation of PD-L1/CD274. Relevant findings were subsequently validated by immunohistochemistry on fixed materials. CRCpMMR contain a significantly increased fraction of CD163+ macrophages (TAMs) expressing TREM2 and CD66+ neutrophils (TANs) together with decrease in CD4−CD8−CD3+ double negative T lymphocytes (DNTs); no differences were revealed by the analysis of conventional and plasmacytoid dendritic cell populations. A fraction of tumor-infiltrating T-cells displays an exhausted phenotype, co-expressing PD-1 and TIM-3. Remarkably, expression of PD-L1 on fresh tumor cells and TAMs was undetectable even after in vitro stimulation with interferon-γ. These findings confirm the immune suppressive microenvironment of CRCpMMR characterized by dense infiltration of TAMs, occurrence of TANs, lack of DNTs, T-cell exhaustion, and interferon-γ unresponsiveness by host and tumor cells. Appropriate bypass strategies should consider these combinations of immune escape mechanisms in CRCpMMR. Full article
(This article belongs to the Special Issue Dendritic Cells in Cancer Immunology and Immunotherapy)
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Review

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14 pages, 1130 KiB  
Review
Ready for Prime Time? Dendritic Cells in High-Grade Gliomas
by Claire A. Conarroe and Timothy N. J. Bullock
Cancers 2023, 15(11), 2902; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15112902 - 25 May 2023
Viewed by 3668
Abstract
High-grade gliomas are malignant brain tumors, and patient outcomes remain dismal despite the emergence of immunotherapies aimed at promoting tumor elimination by the immune system. A robust antitumor immune response requires the presentation of tumor antigens by dendritic cells (DC) to prime cytolytic [...] Read more.
High-grade gliomas are malignant brain tumors, and patient outcomes remain dismal despite the emergence of immunotherapies aimed at promoting tumor elimination by the immune system. A robust antitumor immune response requires the presentation of tumor antigens by dendritic cells (DC) to prime cytolytic T cells. However, there is a paucity of research on dendritic cell activity in the context of high-grade gliomas. As such, this review covers what is known about the role of DC in the CNS, DC infiltration of high-grade gliomas, tumor antigen drainage, the immunogenicity of DC activity, and DC subsets involved in the antitumor immune response. Finally, we consider the implications of suboptimal DC function in the context of immunotherapies and identify opportunities to optimize immunotherapies to treat high-grade gliomas. Full article
(This article belongs to the Special Issue Dendritic Cells in Cancer Immunology and Immunotherapy)
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26 pages, 1654 KiB  
Review
Dendritic Cell Subsets in Melanoma: Pathophysiology, Clinical Prognosis and Therapeutic Exploitation
by Eleonora Sosa Cuevas, Philippe Saas and Caroline Aspord
Cancers 2023, 15(8), 2206; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15082206 - 08 Apr 2023
Cited by 2 | Viewed by 2189
Abstract
Evasion from immunity is a hallmark of cancer development. Dendritic cells (DCs) are strategic immune cells shaping anti-tumor immune responses, but tumor cells exploit DC versatility to subvert their functions. Unveiling the puzzling role of DCs in the control of tumor development and [...] Read more.
Evasion from immunity is a hallmark of cancer development. Dendritic cells (DCs) are strategic immune cells shaping anti-tumor immune responses, but tumor cells exploit DC versatility to subvert their functions. Unveiling the puzzling role of DCs in the control of tumor development and mechanisms of tumor-induced DC hijacking is critical to optimize current therapies and to design future efficient immunotherapies for melanoma. Dendritic cells, crucially positioned at the center of anti-tumor immunity, represent attractive targets to develop new therapeutic approaches. Harnessing the potencies of each DC subset to trigger appropriate immune responses while avoiding their subversion is a challenging yet promising step to achieve tumor immune control. This review focuses on advances regarding the diversity of DC subsets, their pathophysiology and impact on clinical outcome in melanoma patients. We provide insights into the regulation mechanisms of DCs by the tumor, and overview DC-based therapeutic developments for melanoma. Further insights into DCs’ diversity, features, networking, regulation and shaping by the tumor microenvironment will allow designing novel effective cancer therapies. The DCs deserve to be positioned in the current melanoma immunotherapeutic landscape. Recent discoveries strongly motivate exploitation of the exceptional potential of DCs to drive robust anti-tumor immunity, offering promising tracks for clinical successes. Full article
(This article belongs to the Special Issue Dendritic Cells in Cancer Immunology and Immunotherapy)
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24 pages, 770 KiB  
Review
Dendritic-Cell-Vaccine-Based Immunotherapy for Hepatocellular Carcinoma: Clinical Trials and Recent Preclinical Studies
by Long-Bin Jeng, Li-Ying Liao, Fu-Ying Shih and Chiao-Fang Teng
Cancers 2022, 14(18), 4380; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14184380 - 08 Sep 2022
Cited by 10 | Viewed by 2196
Abstract
Although many surgical and nonsurgical therapeutic options have been well-established, hepatocellular carcinoma (HCC) remains the third most common cause of cancer-related death worldwide. Therefore, the discovery of novel potential therapeutic strategies is still urgently required for improving survival and prognosis of HCC patients. [...] Read more.
Although many surgical and nonsurgical therapeutic options have been well-established, hepatocellular carcinoma (HCC) remains the third most common cause of cancer-related death worldwide. Therefore, the discovery of novel potential therapeutic strategies is still urgently required for improving survival and prognosis of HCC patients. As the most potent antigen-presenting cells in the human immune system, dendritic cells (DCs) play an important role in activating not only innate but also adaptive immune responses to specifically destroy tumor cells. As a result, DC-based vaccines, which are prepared by different tumor-antigen-pulsing strategies or maturation-stimulating reagents, either alone or in combination with various anticancer therapies and/or immune effector cells, have been developed as a promising personalized cancer immunotherapy. This review provides a comprehensive summary of the evidence from clinical trials evaluating the safety, feasibility, and efficacy of DC-based vaccines in treating HCC patients and highlights the data from recent preclinical studies regarding the development of promising strategies for optimizing the efficacy of DC-vaccine-based immunotherapy for HCC. Full article
(This article belongs to the Special Issue Dendritic Cells in Cancer Immunology and Immunotherapy)
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