Special Issue "Tumour Associated Dendritic Cells"

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (28 February 2019)

Special Issue Editor

Guest Editor
A/Prof. Dr. Kristen Radford

Mater Research Institute, The University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia
Website | E-Mail
Interests: dendritic cells; cancer immunotherapy; humanised mice

Special Issue Information

Dear Colleagues,

The key role of dendritic cells (DC) in priming adaptive immune responses has long been harnessed for cancer vaccines. Although there is clear evidence that DC vaccines are well tolerated and can induce tumour immune responses, overall they have been of limited clinical benefit. Despite their long history in the clinic, the role of DC in tumour tissue is not well understood and has been confounded by their rarity, heterogeneity and overlapping markers with other myeloid populations. DC can be divided into distinct subsets with highly specialized functions. In a number of mouse tumour models the cDC1 DC subset has been shown to be required for priming anti-tumour immunity and for the efficacy of immunotherapies. These findings reinvigorate manipulation of DC as an attractive strategy to induce or improve immune responses in cancer patients. In this Special Issue, we welcome submissions that will help to build a more complete picture of the role of DC in cancer and particularly welcome submissions on the role of DC subsets in a variety of cancer types, human cancers and new ways in which they may be harnessed to improve tumour immune responses.

A/Prof. Dr. Kristen Radford
Guest Editor

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 papers will be 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.

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Published Papers (5 papers)

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Research

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Open AccessArticle Cord-Blood-Stem-Cell-Derived Conventional Dendritic Cells Specifically Originate from CD115-Expressing Precursors
Cancers 2019, 11(2), 181; https://doi.org/10.3390/cancers11020181
Received: 10 December 2018 / Revised: 30 January 2019 / Accepted: 31 January 2019 / Published: 5 February 2019
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Abstract
Dendritic cells (DCs) are professional antigen-presenting cells which instruct both the innate and adaptive immune systems. Once mature, they have the capacity to activate and prime naïve T cells for recognition and eradication of pathogens and tumor cells. These characteristics make them excellent [...] Read more.
Dendritic cells (DCs) are professional antigen-presenting cells which instruct both the innate and adaptive immune systems. Once mature, they have the capacity to activate and prime naïve T cells for recognition and eradication of pathogens and tumor cells. These characteristics make them excellent candidates for vaccination strategies. Most DC vaccines have been generated from ex vivo culture of monocytes (mo). The use of mo-DCs as vaccines to induce adaptive immunity against cancer has resulted in clinical responses but, overall, treatment success is limited. The application of primary DCs or DCs generated from CD34+ stem cells have been suggested to improve clinical efficacy. Cord blood (CB) is a particularly rich source of CD34+ stem cells for the generation of DCs, but the dynamics and plasticity of the specific DC lineage development are poorly understood. Using flow sorting of DC progenitors from CB cultures and subsequent RNA sequencing, we found that CB-derived DCs (CB-DCs) exclusively originate from CD115+-expressing progenitors. Gene set enrichment analysis displayed an enriched conventional DC profile within the CD115-derived DCs compared with CB mo-DCs. Functional assays demonstrated that these DCs matured and migrated upon good manufacturing practice (GMP)-grade stimulation and possessed a high capacity to activate tumor-antigen-specific T cells. In this study, we developed a culture protocol to generate conventional DCs from CB-derived stem cells in sufficient numbers for vaccination strategies. The discovery of a committed DC precursor in CB-derived stem cell cultures further enables utilization of conventional DC-based vaccines to provide powerful antitumor activity and long-term memory immunity. Full article
(This article belongs to the Special Issue Tumour Associated Dendritic Cells)
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Review

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Open AccessFeature PaperReview A Characterization of Dendritic Cells and Their Role in Immunotherapy in Glioblastoma: From Preclinical Studies to Clinical Trials
Cancers 2019, 11(4), 537; https://doi.org/10.3390/cancers11040537
Received: 20 March 2019 / Revised: 8 April 2019 / Accepted: 12 April 2019 / Published: 15 April 2019
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Abstract
Glioblastoma (GBM) is the most common and fatal primary central nervous system malignancy in adults with a median survival of less than 15 months. Surgery, radiation, and chemotherapy are the standard of care and provide modest benefits in survival, but tumor recurrence is [...] Read more.
Glioblastoma (GBM) is the most common and fatal primary central nervous system malignancy in adults with a median survival of less than 15 months. Surgery, radiation, and chemotherapy are the standard of care and provide modest benefits in survival, but tumor recurrence is inevitable. The poor prognosis of GBM has made the development of novel therapies targeting GBM of paramount importance. Immunotherapy via dendritic cells (DCs) has garnered attention and research as a potential strategy to boost anti-tumor immunity in recent years. As the “professional” antigen processing and presenting cells, DCs play a key role in the initiation of anti-tumor immune responses. Pre-clinical studies in GBM have shown long-term tumor survival and immunological memory in murine models with stimulation of DC activity with various antigens and costimulatory molecules. Phase I and II clinical trials of DC vaccines in GBM have demonstrated some efficacy in improving the median overall survival with minimal to no toxicity with promising initial results from the first Phase III trial. However, there remains no standardization of vaccines in terms of which antigens are used to pulse DCs ex vivo, sites of DC injection, and optimal adjuvant therapies. Future work with DC vaccines aims to elucidate the efficacy of DC-based therapy alone or in combination with other immunotherapy adjuvants in additional Phase III trials. Full article
(This article belongs to the Special Issue Tumour Associated Dendritic Cells)
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Open AccessReview Dendritic Cells and Cancer: From Biology to Therapeutic Intervention
Cancers 2019, 11(4), 521; https://doi.org/10.3390/cancers11040521
Received: 8 March 2019 / Revised: 5 April 2019 / Accepted: 7 April 2019 / Published: 11 April 2019
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Abstract
Inducing effective anti-tumor immunity has become a major therapeutic strategy against cancer. Dendritic cells (DC) are a heterogenous population of antigen presenting cells that infiltrate tumors. While DC play a critical role in the priming and maintenance of local immunity, their functions are [...] Read more.
Inducing effective anti-tumor immunity has become a major therapeutic strategy against cancer. Dendritic cells (DC) are a heterogenous population of antigen presenting cells that infiltrate tumors. While DC play a critical role in the priming and maintenance of local immunity, their functions are often diminished, or suppressed, by factors encountered in the tumor microenvironment. Furthermore, DC populations with immunosuppressive activities are also recruited to tumors, limiting T cell infiltration and promoting tumor growth. Anti-cancer therapies can impact the function of tumor-associated DC and/or alter their phenotype. Therefore, the design of effective anti-cancer therapies for clinical translation should consider how best to boost tumor-associated DC function to drive anti-tumor immunity. In this review, we discuss the different subsets of tumor-infiltrating DC and their role in anti-tumor immunity. Moreover, we describe strategies to enhance DC function within tumors and harness these cells for effective tumor immunotherapy. Full article
(This article belongs to the Special Issue Tumour Associated Dendritic Cells)
Open AccessReview Immunology of Plasmacytoid Dendritic Cells in Solid Tumors: A Brief Review
Cancers 2019, 11(4), 470; https://doi.org/10.3390/cancers11040470
Received: 28 February 2019 / Revised: 30 March 2019 / Accepted: 1 April 2019 / Published: 3 April 2019
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Abstract
The immune response, both innate and adaptive, is a key player in cancer development and progression. Plasmacytoid dendritic cells (pDCs) are a subset of dendritic cells that play one of the central roles in the immune system. They are known mostly as the [...] Read more.
The immune response, both innate and adaptive, is a key player in cancer development and progression. Plasmacytoid dendritic cells (pDCs) are a subset of dendritic cells that play one of the central roles in the immune system. They are known mostly as the major IFN type I-producing cells upon stimulation of Toll-like receptors 7 and 9. However, based on current knowledge, the functionality of pDCs is very complex, as they have the ability to affect many other cell types. In the context of the tumor tissue, pDCs were mostly described to show substantial functional defects and therefore contribute to the establishement of immunosuppressive tumor microenvironment. Immunotherapeutic approaches have proven to be one of the most promising treatment strategies in the last decade. In view of this fact, it is crucial to map the complexity of the tumor microenvironment in detail, including less numerous cell types. This review focuses on pDCs in relation to solid tumors. We provide a summary of current data on the role of pDCs in different tumor types and suggest their possible clinical applications. Full article
(This article belongs to the Special Issue Tumour Associated Dendritic Cells)
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Open AccessReview Use of Dendritic Cell Receptors as Targets for Enhancing Anti-Cancer Immune Responses
Cancers 2019, 11(3), 418; https://doi.org/10.3390/cancers11030418
Received: 27 February 2019 / Accepted: 19 March 2019 / Published: 24 March 2019
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Abstract
A successful anti-cancer vaccine construct depends on its ability to induce humoral and cellular immunity against a specific antigen. Targeting receptors of dendritic cells to promote the loading of cancer antigen through an antibody-mediated antigen uptake mechanism is a promising strategy in cancer [...] Read more.
A successful anti-cancer vaccine construct depends on its ability to induce humoral and cellular immunity against a specific antigen. Targeting receptors of dendritic cells to promote the loading of cancer antigen through an antibody-mediated antigen uptake mechanism is a promising strategy in cancer immunotherapy. Researchers have been targeting different dendritic cell receptors such as Fc receptors (FcR), various C-type lectin-like receptors such as dendritic and thymic epithelial cell-205 (DEC-205), dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), and Dectin-1 to enhance the uptake process and subsequent presentation of antigen to T cells through major histocompatibility complex (MHC) molecules. In this review, we compare different subtypes of dendritic cells, current knowledge on some important receptors of dendritic cells, and recent articles on targeting those receptors for anti-cancer immune responses in mouse models. Full article
(This article belongs to the Special Issue Tumour Associated Dendritic Cells)
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