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Cancers
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Development of Immunotherapy Using Dendritic Cells and Development of Therapeutic...
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Development of Immunotherapy Using Dendritic Cells and Development of Therapeutic Strategy targeting Hedgehog Signaling

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

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 5643

Special Issue Editor

Dr. Hideya Onishi

E-Mail Website
Guest Editor
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Interests: immunotherapy; cancer vaccination; developing cancer therapy targeting morphogenesis signaling; cancer and hypoxia

Special Issue Information

Dear Colleagues,

Recently, progress in cancer immunotherapy has been remarkable after the startup stage of cancer peptide vaccines and dendritic cell vaccines. New therapeutic strategies, such as immune checkpoint inhibitor, chimeric antigen receptor T-cell therapy, photoimmunotherapy, and vaccine therapy using neoantigen peptide which arises from a mutation in cancers, are developing one after another. Useful biomarkers for the measurement of the effect of immunotherapy and the agents that augment the effect of immune checkpoint inhibitors are attracting much attention.

On the other hand, hedgehog (Hh) signaling that is morphogenesis signaling is shown to be re-activated in cancers to induce cancer malignant phenotype. Some authors showed that Hh signaling contributes to the maintenance of cancer stem cells. In addition, it has been revealed that Hh signaling is activated in the hypoxic condition, which is a cancer microenvironment, and that Hh signaling is involved in cancer fibrosis and PD-L1 expression to inhibit immune response. The development of cancer therapy targeting Hh signaling has been performed in several solid cancers.

This Special Issue, to fight against refractory solid cancers, focuses on 2 aspects: cancer immunotherapy and cancer therapy with Hh signaling inhibition.

Dr. Hideya Onishi
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 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

  • New Immunotherapy
  • Neoantigen
  • Dendritic cells
  • Hedgehog signaling
  • Induction of malignant
  • phenotypes
  • Cancer microenvironment
  • Hypoxia
  • Clinical trial

Published Papers (2 papers)

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Research

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18 pages, 4767 KiB  
Article
Alpha-Fetoprotein- and CD40Ligand-Expressing Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma
by Annabelle Vogt, Farsaneh Sadeghlar, Tiyasha H. Ayub, Carlo Schneider, Christian Möhring, Taotao Zhou, Robert Mahn, Alexandra Bartels, Michael Praktiknjo, Miroslaw T. Kornek, Marieta Toma, Ingo G. H. Schmidt-Wolf, Vittorio Branchi, Hanno Matthaei, Jörg C. Kalff, Christian P. Strassburg and Maria A. Gonzalez-Carmona
Cancers 2021, 13(13), 3375; https://doi.org/10.3390/cancers13133375 - 05 Jul 2021
Cited by 13 | Viewed by 2284
Abstract
Dendritic cells (DC) as professional antigen presenting cells are able to prime T-cells against the tumor-associated antigen α-fetoprotein (AFP) for immunotherapy of hepatocellular carcinoma (HCC). However, a strong immunosuppressive tumor environment limits their efficacy in patients. The co-stimulation with CD40Ligand (CD40L) is critical [...] Read more.
Dendritic cells (DC) as professional antigen presenting cells are able to prime T-cells against the tumor-associated antigen α-fetoprotein (AFP) for immunotherapy of hepatocellular carcinoma (HCC). However, a strong immunosuppressive tumor environment limits their efficacy in patients. The co-stimulation with CD40Ligand (CD40L) is critical in the maturation of DC and T-cell priming. In this study, the impact of intratumoral (i.t.) CD40L-expressing DC to improve vaccination with murine (m)AFP-transduced DC (Ad-mAFP-DC) was analyzed in subcutaneous (s.c.) and orthotopic murine HCC. Murine DC were adenovirally transduced with Ad-mAFP or Ad-CD40L. Hepa129-mAFP-cells were injected into the right flank or the liver of C3H-mice to induce subcutaneous (s.c.) and orthotopic HCC. For treatments, 106 Ad-mAFP-transduced DC were inoculated s.c. followed by 106 CD40L-expressing DC injected intratumorally (i.t.). S.c. inoculation with Ad-mAFP-transduced DC, as vaccine, induced a delay of tumor-growth of AFP-positive HCC compared to controls. When s.c.-inoculation of Ad-mAFP-DC was combined with i.t.-application of Ad-CD40L-DC synergistic antitumoral effects were observed and complete remissions and long-term survival in 62% of tumor-bearing animals were achieved. Analysis of the tumor environment at different time points revealed that s.c.-vaccination with Ad-mAFP-DC seems to stimulate tumor-specific effector cells, allowing an earlier recruitment of effector T-cells and a Th1 shift within the tumors. After i.t. co-stimulation with Ad-CD40L-DC, production of Th1-cytokines was strongly increased and accompanied by a robust tumor infiltration of mature DC, activated CD4+-, CD8+-T-cells as well as reduction of regulatory T-cells. Moreover, Ad-CD40L-DC induced tumor cell apoptosis. Intratumoral co-stimulation with CD40L-expressing DC significantly improves vaccination with Ad-mAFP-DC in pre-established HCC in vivo. Combined therapy caused an early and strong Th1-shift in the tumor environment as well as higher tumor apoptosis, leading to synergistic tumor regression of HCC. Thus, CD40L co-stimulation represents a promising tool for improving DC-based immunotherapy of HCC. Full article
(This article belongs to the Special Issue Development of Immunotherapy Using Dendritic Cells and Development of Therapeutic Strategy targeting Hedgehog Signaling)
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Review

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14 pages, 2077 KiB  
Review
Lymph Nodes as Anti-Tumor Immunotherapeutic Tools: Intranodal-Tumor-Specific Antigen-Pulsed Dendritic Cell Vaccine Immunotherapy
by Takashi Morisaki, Takafumi Morisaki, Makoto Kubo, Shinji Morisaki, Yusuke Nakamura and Hideya Onishi
Cancers 2022, 14(10), 2438; https://doi.org/10.3390/cancers14102438 - 15 May 2022
Cited by 6 | Viewed by 2514
Abstract
Hundreds of lymph nodes (LNs) are scattered throughout the body. Although each LN is small, it represents a complete immune organ that contains almost all types of immunocompetent and stromal cells functioning as scaffolds. In this review, we highlight the importance of LNs [...] Read more.
Hundreds of lymph nodes (LNs) are scattered throughout the body. Although each LN is small, it represents a complete immune organ that contains almost all types of immunocompetent and stromal cells functioning as scaffolds. In this review, we highlight the importance of LNs in cancer immunotherapy. First, we review recent reports on structural and functional properties of LNs as sites for antitumor immunity and discuss their therapeutic utility in tumor immunotherapy. Second, we discuss the rationale and background of ultrasound (US)-guided intranodal injection methods. In addition, we review intranodal administration therapy of tumor-specific-antigen-pulsed matured dendritic cells (DCs), including neoantigen-pulsed vaccines. Full article
(This article belongs to the Special Issue Development of Immunotherapy Using Dendritic Cells and Development of Therapeutic Strategy targeting Hedgehog Signaling)
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