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Veterinary Sciences
Special Issues
Canine Cancer Immunology and Immunotherapeutic
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Canine Cancer Immunology and Immunotherapeutic

A special issue of Veterinary Sciences (ISSN 2306-7381). This special issue belongs to the section "Veterinary Microbiology, Parasitology and Immunology".

Deadline for manuscript submissions: closed (15 May 2023) | Viewed by 12365

Special Issue Editors

Dr. Ellen E. Sparger

E-Mail Website
Guest Editor
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
Interests: molecular pathogenesis of feline immunodeficiency virus infection; vaccine development in animal models for HIV-1 AIDS; use of cytokines and TLR ligands as vaccine adjuvants; tumor immunology in companion animal cancer
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Steven Dow

E-Mail Website
Guest Editor
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA
Interests: developing new immunotherapies to treat cancer; cancer vaccines; repurposed immunotherapy drugs; checkpoint targeted immunotherapies
Dr. Sita Withers

E-Mail Website
Guest Editor
Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA
Interests: comparative cancer immunology; immunotherapy; canine T-lymphocyte subsets; tumor associated macrophages; tumor microenvironment; metastasis; osteosarcoma

Special Issue Information

Dear Colleagues,

Reports over the past decade have shown that agents that activate the immune system by blocking specific anti-inflammatory check points, as well as engineered T cells, have proven to be effective in certain human cancer patient populations. Based on similar strategies and in some cases more novel approaches, canine-specific immunotherapeutics have been recently described and more are in the development pipeline. Canine immunotherapeutics in current investigations include monoclonal antibodies that target immune checkpoints and cancer-specific antigens, oncolytic viruses, nonspecific immunodulators including cytokines and ligands for pattern recognition receptors (PPRs), cancer vaccines, and T cell therapy, such as chimeric antigen receptor (CAR) T cells. Such therapeutic modalities carry the potential to significantly impact treatment protocols for certain canine cancers as well as human cancer in the future and therefore present an area of focus for clinical canine cancer research.

This Special Issue aims to report the current progress in the characterization of canine cancer immune profiles and the development of canine cancer immunotherapeutic strategies and protocols. In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: development of diagnostic agents for the recognition of canine cancer-related immune markers, characterization of canine cancer-related immune profiles particularly to guide selection of patients for specific immunotherapeutics, and development and testing of canine cancer immunotherapeutics.

We look forward to receiving your contributions. 

Dr. Ellen E. Sparger
Prof. Dr. Steven Dow
Dr. Sita Withers
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. Veterinary Sciences 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

  • canine cancer
  • cancer immunotherapeutics
  • animal models
  • checkpoint inhibitors
  • engineered T cells
  • cancer vaccines
  • cancer-related immune profiles
  • immune modulation in cancer
  • immunotherapy toxicities
  • One Health
  • One Medicine

Published Papers (4 papers)

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Research

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16 pages, 2492 KiB  
Article
Intra- and Intertumoral Microglia/Macrophage Infiltration and Their Associated Molecular Signature Is Highly Variable in Canine Oligodendroglioma: A Preliminary Evaluation
by Ryan G. Toedebusch, Ning-Wei Wei, Kulani T. Simafranca, Jennie A. Furth-Jacobus, Ingrid Brust-Mascher, Susan L. Stewart, Peter J. Dickinson, Kevin D. Woolard, Chai-Fei Li, Karen M. Vernau, Frederick J. Meyers and Christine M. Toedebusch
Vet. Sci. 2023, 10(6), 403; https://doi.org/10.3390/vetsci10060403 - 19 Jun 2023
Viewed by 1829
Abstract
The goal of this study was to define the glioma-associated microglia/macrophage (GAM) response and associated molecular landscape in canine oligodendrogliomas. Here, we quantified the intratumoral GAM density of low- and high-grade oligodendrogliomas compared to that of a normal brain, as well as the [...] Read more.
The goal of this study was to define the glioma-associated microglia/macrophage (GAM) response and associated molecular landscape in canine oligodendrogliomas. Here, we quantified the intratumoral GAM density of low- and high-grade oligodendrogliomas compared to that of a normal brain, as well as the intratumoral concentration of several known GAM-derived pro-tumorigenic molecules in high-grade oligodendrogliomas compared to that in a normal brain. Our analysis demonstrated marked intra- and intertumoral heterogeneity of GAM infiltration. Correspondingly, we observed significant variability in the intratumoral concentrations of several GAM-associated molecules, unlike what we previously observed in high-grade astrocytomas. However, high-grade oligodendroglioma tumor homogenates (n = 6) exhibited an increase in the pro-tumorigenic molecules hepatocyte growth factor receptor (HGFR) and vascular endothelial growth factor (VEGF), as we observed in high-grade astrocytomas. Moreover, neoplastic oligodendrocytes displayed robust expression of GAL-3, a chimeric galectin implicated in driving immunosuppression in human glioblastoma. While this work identifies shared putative therapeutic targets across canine glioma subtypes (HGFR, GAL-3), it highlights several key differences in the immune landscape. Therefore, a continued effort to develop a comprehensive understanding of the immune microenvironment within each subtype is necessary to inform therapeutic strategies going forward. Full article
(This article belongs to the Special Issue Canine Cancer Immunology and Immunotherapeutic)
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13 pages, 1805 KiB  
Article
The Effect of Arginase on Canine T-Lymphocyte Functions and its Modulation by All-Trans Retinoid Acid (ATRA) in Canine Monocyte-Derived Macrophages
by Aimee M. Soileau, Cally N. Quick, Cambri E. Moeller, Jessica C. Schaumburg and Sita S. Withers
Vet. Sci. 2022, 9(7), 374; https://doi.org/10.3390/vetsci9070374 - 21 Jul 2022
Cited by 1 | Viewed by 2125
Abstract
Immunosuppressive myeloid cells in the tumor microenvironment play a major role in suppressing tumor immunity via the production of arginase, IL-10, and others. The objectives of this study were to determine the ability of all-trans retinoic acid (ATRA) to decrease the expression of [...] Read more.
Immunosuppressive myeloid cells in the tumor microenvironment play a major role in suppressing tumor immunity via the production of arginase, IL-10, and others. The objectives of this study were to determine the ability of all-trans retinoic acid (ATRA) to decrease the expression of arginase and other soluble mediators by canine monocyte-derived macrophages (MDMs) and to determine the inhibitory activity of arginase on canine T-lymphocytes. The immunomodulatory ability of ATRA (2 µM) on canine MDMs was evaluated via reverse transcription quantitative PCR (RT-qPCR), flow cytometry, arginase activity assay, and enzyme-linked immunoassay (ELISA). Arginase effects on T-lymphocyte phenotype and proliferation were then evaluated by flow cytometry. ATRA consistently decreased MDM expression of IL6, TGFB1, NOS2, ARG1, and CIITA transcripts, by approximately 2–4-fold, although this did not reach statistical significance for ARG1 or CIITA. Furthermore, arginase activity was decreased in ATRA-treated MDMs while the MDM phenotype remained unchanged. Arginase decreased the expression of granzyme B on CD8+ T-lymphocytes and inhibited CD4+ and CD8+ T-lymphocyte proliferation. These findings suggested that ATRA could inhibit canine MDM production of soluble inflammatory/immunosuppressive mediators. These data also revealed that arginase decreased canine T-lymphocyte proliferation and granzyme B expression. Further studies are needed to determine whether ATRA could reverse the immunosuppressive effects of myeloid cells on canine T-lymphocytes in vivo. Full article
(This article belongs to the Special Issue Canine Cancer Immunology and Immunotherapeutic)
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16 pages, 2807 KiB  
Article
Safety and Efficacy of an Oncolytic Adenovirus as an Immunotherapy for Canine Cancer Patients
by Clara Martín-Carrasco, Pablo Delgado-Bonet, Beatriz Davinia Tomeo-Martín, Josep Pastor, Claudia de la Riva, Paula Palau-Concejo, Noemí del Castillo, Javier García-Castro and Ana Judith Perisé-Barrios
Vet. Sci. 2022, 9(7), 327; https://doi.org/10.3390/vetsci9070327 - 28 Jun 2022
Cited by 6 | Viewed by 3186
Abstract
The use of oncolytic viruses is an innovative approach to lyse tumor cells and induce antitumor immune responses. Eight dogs diagnosed with carcinoma/adenocarcinoma were intratumorally treated with ICOCAV15, an oncolytic canine adenovirus (CAV). To evaluate the treatment’s safety, a blood count, biochemistry, and [...] Read more.
The use of oncolytic viruses is an innovative approach to lyse tumor cells and induce antitumor immune responses. Eight dogs diagnosed with carcinoma/adenocarcinoma were intratumorally treated with ICOCAV15, an oncolytic canine adenovirus (CAV). To evaluate the treatment’s safety, a blood count, biochemistry, and coagulation test were performed before treatment and during follow-up. Immune populations were analyzed by flow cytometry. Anti-adenovirus antibodies were also determined. The immune infiltration, vascularization, and viral presence in the tumor were determined by CD3, CD4, CD20, CD31 and CAV by immunohistochemistry. All the dogs maintained a good quality of life during follow-up, and some had increased median survival time when compared with dogs treated with chemotherapy. No treatment-related adverse effects were detected. The Response Evaluation Criteria In Solid Tumors criteria were also assessed: two patients showed a partial response and the rest showed stable disease at various times during the study. ICOCAV15 was detected inside the tumor during follow-up, and antiviral antibodies were detected in all patients. Furthermore, the tumor-infiltrating immune cells increased after viral administration. Therefore, we suggest that intratumorally administered ICOCAV15 could represent as a new tool for the treatment of canine carcinoma because it is safe, well-tolerated by dogs, and shows promising results. Full article
(This article belongs to the Special Issue Canine Cancer Immunology and Immunotherapeutic)
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Review

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22 pages, 1615 KiB  
Review
The Novel Diagnostic Techniques and Biomarkers of Canine Mammary Tumors
by Ilona Kaszak, Olga Witkowska-Piłaszewicz, Kinga Domrazek and Piotr Jurka
Vet. Sci. 2022, 9(10), 526; https://doi.org/10.3390/vetsci9100526 - 26 Sep 2022
Cited by 9 | Viewed by 4226
Abstract
Canine mammary tumors (CMTs) are considered a serious clinical problem in older bitches. Due to the high malignancy rate and poor prognosis, an early diagnosis is essential. This article is a summary of novel diagnostic techniques as well as the main biomarkers of [...] Read more.
Canine mammary tumors (CMTs) are considered a serious clinical problem in older bitches. Due to the high malignancy rate and poor prognosis, an early diagnosis is essential. This article is a summary of novel diagnostic techniques as well as the main biomarkers of CMTs. So far, CMTs are detected only when changes in mammary glands are clinically visible and surgical removal of the mass is the only recommended treatment. Proper diagnostics of CMT is especially important as they represent a very diverse group of tumors and therefore different treatment approaches may be required. Recently, new diagnostic options appeared, like a new cytological grading system of CMTs or B-mode ultrasound, the Doppler technique, contrast-enhanced ultrasound, and real-time elastography, which may be useful in pre-surgical evaluation. However, in order to detect malignancies before macroscopic changes are visible, evaluation of serum and tissue biomarkers should be considered. Among them, we distinguish markers of the cell cycle, proliferation, apoptosis, metastatic potential and prognosis, hormone receptors, inflammatory and more recent: metabolomic, gene expression, miRNA, and transcriptome sequencing markers. The use of a couple of the above-mentioned markers together seems to be the most useful for the early diagnosis of neoplastic diseases as well as to evaluate response to treatment, presence of tumor progression, or further prognosis. Molecular aspects of tumors seem to be crucial for proper understanding of tumorigenesis and the application of individual treatment options. Full article
(This article belongs to the Special Issue Canine Cancer Immunology and Immunotherapeutic)
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