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Biomedicines
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Dendritic Cells and Cancer Immunotherapy
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Dendritic Cells and Cancer Immunotherapy

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 May 2016) | Viewed by 39721

Special Issue Editors

Dr. Stanleyson Hato

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Guest Editor
Department of Tumor Immunology, Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
Interests: cancer immunotherapy; suppressive tumor microenvironment; signaling networks; immunogenic cell death
Dr. Ghaith Bakdash

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Guest Editor
Department of Tumor Immunology, Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
Interests: dendritic cells, immunotherapy, tumor microenvironment, T cell polarization, immune tolerance

Special Issue Information

Dear Colleagues,

Dendritic cells (DCs) are a specialized population of professional antigen-presenting cells that play a crucial role in the induction of adaptive immune responses and in the maintenance of peripheral tolerance. As initiators of antigen-specific immune responses, DCs are imperative in establishing anti-tumor adaptive immune responses. This role has been exploited for therapeutic purposes in various anti-tumor vaccination strategies. Over the years, many insights into the qualities and functions of DCs have been gained. This acquired knowledge has been translated into improved DC-based vaccines through the better selection of DC subtypes for vaccine preparation and the optimization of peptide selection, loading strategies, and routes of administration. Until now, anti-tumor DC vaccines have only proven efficacious in a small population of cancer patients.

Therefore, this Special Issue on dendritic cell vaccines will focus on strategies for improving DC vaccination in combination with other therapies, such as checkpoint inhibitors, chemotherapy, or radiation therapy, that alter the tumor microenvironment. Of particular interest will be manuscripts discussing the use of DC vaccines in prophylactic or adjuvant settings through the targeting of cancer stem cells or dormant tumor cells. Manuscripts describing the accumulation DC subtypes in the tumor environment and how they might be targeted for therapeutic benefit are also welcome. This Special Issue will include original research, review articles, commentaries, and editorials discussing the use of DC vaccines in cancer immunotherapy. Topics of interest for this Special Issue include, but are not limited to, the key words listed below.

Dr. Stanleyson Hato
Dr. Ghaith Bakdash
Guest Editors

Manuscript Submission Information

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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. Biomedicines is an international peer-reviewed open access monthly 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 2600 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

  • DC-based anti-cancer vaccines
  • DC vaccines combinded with checkpoint inhibitors
  • DC vaccines combinded with chemotherapy or small molecule inhibitors
  • DC maturation/activation and tumor-associated “danger” signals
  • Cross-presentation of tumor antigens
  • The role of DC in the induction of tumor-specific T cell responses
  • The influence of tumor-derived factors on DC differentiation, maturation, activation, and function
  • Immunosuppression by immature myeloid cells such as myeloid-derived suppressor cells
  • Regulatory DCs and cancer

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Published Papers (5 papers)

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Research

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5533 KiB  
Article
Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques
by Bryan C. Au, Chyan-Jang Lee, Orlay Lopez-Perez, Warren Foltz, Tania C. Felizardo, James C.M. Wang, Ju Huang, Xin Fan, Melissa Madden, Alyssa Goldstein, David A. Jaffray, Badru Moloo, J. Andrea McCart and Jeffrey A. Medin
Biomedicines 2016, 4(1), 6; https://doi.org/10.3390/biomedicines4010006 - 19 Feb 2016
Cited by 2 | Viewed by 5839
Abstract
Anti-cancer immunotherapy is emerging from a nadir and demonstrating tangible benefits to patients. A variety of approaches are now employed. We are invoking antigen (Ag)-specific responses through direct injections of recombinant lentivectors (LVs) that encode sequences for tumor-associated antigens into multiple lymph nodes [...] Read more.
Anti-cancer immunotherapy is emerging from a nadir and demonstrating tangible benefits to patients. A variety of approaches are now employed. We are invoking antigen (Ag)-specific responses through direct injections of recombinant lentivectors (LVs) that encode sequences for tumor-associated antigens into multiple lymph nodes to optimize immune presentation/stimulation. Here we first demonstrate the effectiveness and antigen-specificity of this approach in mice challenged with prostate-specific antigen (PSA)-expressing tumor cells. Next we tested the safety and efficacy of this approach in two cohorts of rhesus macaques as a prelude to a clinical trial application. Our vector encodes the cDNA for rhesus macaque PSA and a rhesus macaque cell surface marker to facilitate vector titering and tracking. We utilized two independent injection schemas demarcated by the timing of LV administration. In both cohorts we observed marked tissue-specific responses as measured by clinical evaluations and magnetic resonance imaging of the prostate gland. Tissue-specific responses were sustained for up to six months—the end-point of the study. Control animals immunized against an irrelevant Ag were unaffected. We did not observe vector spread in test or control animals or perturbations of systemic immune parameters. This approach thus offers an “off-the-shelf” anti-cancer vaccine that could be made at large scale and injected into patients—even on an out-patient basis. Full article
(This article belongs to the Special Issue Dendritic Cells and Cancer Immunotherapy)
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1202 KiB  
Article
Enzyme-Linked Immunosorbent Spot Assay for the Detection of Wilms’ Tumor 1-Specific T Cells Induced by Dendritic Cell Vaccination
by Yumiko Higuchi, Terutsugu Koya, Miki Yuzawa, Naoko Yamaoka, Yumiko Mizuno, Kiyoshi Yoshizawa, Koichi Hirabayashi, Takashi Kobayashi, Kenji Sano and Shigetaka Shimodaira
Biomedicines 2015, 3(4), 304-315; https://doi.org/10.3390/biomedicines3040304 - 4 Dec 2015
Cited by 11 | Viewed by 5338
Abstract
Background: Despite recent advances in cancer immunotherapy and the development of various assays for T cell assessment, a lack of universal standards within immune monitoring remains. The objective of this study was to evaluate the enzyme-linked immunosorbent spot (ELISpot) assay in comparison with [...] Read more.
Background: Despite recent advances in cancer immunotherapy and the development of various assays for T cell assessment, a lack of universal standards within immune monitoring remains. The objective of this study was to evaluate the enzyme-linked immunosorbent spot (ELISpot) assay in comparison with major histocompatibility complex-tetramer analysis in the context of dendritic cell (DC)-based cancer immunotherapy. Methods: The ELISpot assay was performed on peripheral blood mononuclear cells to assess reproducibility, daily precision, and linearity using HLA-A*24:02-restricted Cytomegalovirus peptide. Wilms’ tumor 1 (WT1) antigen-specific cytotoxic T cells were then evaluated by both the ELISpot assay and WT1 tetramer analysis in peripheral blood from 46 cancer patients who received DC vaccinations pulsed with human leukocyte antigen (HLA)-A*24:02-restricted modified WT1 peptides. Results: The ELISpot assay was proven to have reproducibility (coefficient of variation (CV) ranged from 7.4% to 16.3%), daily precision (CV ranged from 5.0% to 17.3%), and linearity (r = 0.96–0.98). WT1-specific immune responses were detected by the ELISpot assay in 34 out of 46 patients (73.9%) post-vaccination. A Spearman’s rank-correlation coefficient of 0.82 between the ELISpot assay and WT1 tetramer analysis was obtained. Conclusion: This is the first report of a comparison of an ELISpot assay and tetramer analysis in the context of dendritic cell (DC)-based cancer immunotherapy. The ELISpot assay has reproducibility, linearity, and excellent correlation with the WT1 tetramer analysis. These findings suggest that the validated ELISpot assay is useful to monitor the acquired immunity by DC vaccination targeting WT1. Full article
(This article belongs to the Special Issue Dendritic Cells and Cancer Immunotherapy)
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Review

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1351 KiB  
Review
Cancer Vaccines in Ovarian Cancer: How Can We Improve?
by Silvia Martin Lluesma, Anita Wolfer, Alexandre Harari and Lana E. Kandalaft
Biomedicines 2016, 4(2), 10; https://doi.org/10.3390/biomedicines4020010 - 3 May 2016
Cited by 49 | Viewed by 9821
Abstract
Epithelial ovarian cancer (EOC) is one important cause of gynecologic cancer-related death. Currently, the mainstay of ovarian cancer treatment consists of cytoreductive surgery and platinum-based chemotherapy (introduced 30 years ago) but, as the disease is usually diagnosed at an advanced stage, its prognosis [...] Read more.
Epithelial ovarian cancer (EOC) is one important cause of gynecologic cancer-related death. Currently, the mainstay of ovarian cancer treatment consists of cytoreductive surgery and platinum-based chemotherapy (introduced 30 years ago) but, as the disease is usually diagnosed at an advanced stage, its prognosis remains very poor. Clearly, there is a critical need for new treatment options, and immunotherapy is one attractive alternative. Prophylactic vaccines for prevention of infectious diseases have led to major achievements, yet therapeutic cancer vaccines have shown consistently low efficacy in the past. However, as they are associated with minimal side effects or invasive procedures, efforts directed to improve their efficacy are being deployed, with Dendritic Cell (DC) vaccination strategies standing as one of the more promising options. On the other hand, recent advances in our understanding of immunological mechanisms have led to the development of successful strategies for the treatment of different cancers, such as immune checkpoint blockade strategies. Combining these strategies with DC vaccination approaches and introducing novel combinatorial designs must also be considered and evaluated. In this review, we will analyze past vaccination methods used in ovarian cancer, and we will provide different suggestions aiming to improve their efficacy in future trials. Full article
(This article belongs to the Special Issue Dendritic Cells and Cancer Immunotherapy)
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615 KiB  
Review
Innate Lymphoid Cells in Tumor Immunity
by Jasper J. P. Van Beek, Anne W. J. Martens, Ghaith Bakdash and I. Jolanda M. De Vries
Biomedicines 2016, 4(1), 7; https://doi.org/10.3390/biomedicines4010007 - 25 Feb 2016
Cited by 26 | Viewed by 8055
Abstract
Innate lymphoid cells (ILCs) are a group of immune cells of the lymphoid lineage that do not possess antigen specificity. The group includes natural killer (NK) cells, lymphoid tissue inducer (LTi) cells and the recently identified ILC1s, ILC2s and ILC3s. Although the role [...] Read more.
Innate lymphoid cells (ILCs) are a group of immune cells of the lymphoid lineage that do not possess antigen specificity. The group includes natural killer (NK) cells, lymphoid tissue inducer (LTi) cells and the recently identified ILC1s, ILC2s and ILC3s. Although the role of NK cells in the context of cancer has been well established, the involvement of other ILC subsets in cancer progression and resistance is just emerging. Here, we review the literature on the role of the different ILC subsets in tumor immunity and discuss its implications for cancer treatment and monitoring. Full article
(This article belongs to the Special Issue Dendritic Cells and Cancer Immunotherapy)
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1303 KiB  
Review
Primary Human Blood Dendritic Cells for Cancer Immunotherapy—Tailoring the Immune Response by Dendritic Cell Maturation
by Simone P. Sittig, I. Jolanda M. De Vries and Gerty Schreibelt
Biomedicines 2015, 3(4), 282-303; https://doi.org/10.3390/biomedicines3040282 - 2 Dec 2015
Cited by 21 | Viewed by 9943
Abstract
Dendritic cell (DC)-based cancer vaccines hold the great promise of tipping the balance from tolerance of the tumor to rejection. In the last two decades, we have gained tremendous knowledge about DC-based cancer vaccines. The maturation of DCs has proven indispensable to induce [...] Read more.
Dendritic cell (DC)-based cancer vaccines hold the great promise of tipping the balance from tolerance of the tumor to rejection. In the last two decades, we have gained tremendous knowledge about DC-based cancer vaccines. The maturation of DCs has proven indispensable to induce immunogenic T cell responses. We review the insights gained from the development of maturation cocktails in monocyte derived DC-based trials. More recently, we have also gained insights into the functional specialization of primary human blood DC subsets. In peripheral human blood, we can distinguish at least three primary DC subsets, namely CD1c+ and CD141+ myeloid DCs and plasmacytoid DCs. We reflect the current knowledge on maturation and T helper polarization by these blood DC subsets in the context of DC-based cancer vaccines. The maturation stimulus in combination with the DC subset will determine the type of T cell response that is induced. First trials with these natural DCs underline their excellent in vivo functioning and mark them as promising tools for future vaccination strategies. Full article
(This article belongs to the Special Issue Dendritic Cells and Cancer Immunotherapy)
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