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Animals
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Cancer Immunotherapy Research in Veterinary Medicine
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Cancer Immunotherapy Research in Veterinary Medicine

A special issue of Animals (ISSN 2076-2615). This special issue belongs to the section "Veterinary Clinical Studies".

Deadline for manuscript submissions: closed (31 January 2025) | Viewed by 6825

Special Issue Editors

Dr. Francesca Millanta

E-Mail Website
Guest Editor
Department of Veterinary Sciences, University of Pisa, Pisa, Italy
Interests: veterinary oncology; histopathology; veterinary general pathology; comparative pathology; cancer biomarkers; cancer immunology
Dr. Francesca Parisi

E-Mail Website
Guest Editor
Department of Veterinary Sciences, University of Pisa, 56126 Pisa, Italy
Interests: veterinary pathology; comparative pathology; veterinary oncology; histopathology; cancer immunology; cancer biomarkers; veterinary anatomic pathology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Immunotherapy has revolutionized cancer treatment and has become an increasingly important approach in human oncology. The main fields of immunotherapy include the study of the immune system role in tumor progression and their dynamic interaction, the tumor microenvironment, the development, and the use of therapies stimulating the immune system to elicit an anti-tumoral response. Based on the underlying mechanism, different categories of immunotherapy have been developed in cancer treatment, such as cancer vaccines, immune checkpoint inhibitors (es PD-1 and CTLA-4), adoptive transfer of engineered cells (such as T-cells, natural killer cells or macrophages), cytokine therapies, monoclonal antibodies as therapeutic agents, and oncolytic virotherapy.

The purpose of this Special Issue is to focus on immunotherapy approaches in veterinary medicine, involving pathological, clinical, and translational studies on immunotherapy biomarkers, immunology signaling pathways, and novel immunotherapies.

Dr. Francesca Millanta
Dr. Francesca Parisi
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. Animals 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 2400 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

  • cancer
  • immunobiomarkers
  • immunotherapy
  • immune signal pathways
  • immune system
  • veterinary oncology

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Published Papers (5 papers)

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Research

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20 pages, 5310 KiB  
Article
Breed-Associated Differences in Differential Gene Expression Following Immunotherapy-Based Treatment of Canine High-Grade Glioma
by Susan A. Arnold, Walter C. Low and Grace Elizabeth Pluhar
Animals 2025, 15(1), 28; https://doi.org/10.3390/ani15010028 - 26 Dec 2024
Viewed by 693
Abstract
Canine high-grade glioma (HGG) is among the deadliest and most treatment-resistant forms of canine cancer. Successful, widespread treatment is challenged by heterogeneity in tumor cells and the tumor microenvironment and tumor evolution following treatment. Immunotherapy is theoretically a strong novel therapy, since HGG-generated [...] Read more.
Canine high-grade glioma (HGG) is among the deadliest and most treatment-resistant forms of canine cancer. Successful, widespread treatment is challenged by heterogeneity in tumor cells and the tumor microenvironment and tumor evolution following treatment. Immunotherapy is theoretically a strong novel therapy, since HGG-generated immunosuppression is a substantial malignancy mechanism. Immunotherapy has improved survival times overall, but has been associated with extremely poor outcomes in French bulldogs. Given this breed-specific observation, we hypothesized that within the French bulldog breed, there are key transcriptomic differences when compared to other breeds, and that their tumors change differently in response to immunotherapy. Using bulk RNA sequencing, French bulldog tumors were confirmed to differ substantially from boxer and Boston terrier tumors, with only 15.9% overlap in significant differentially expressed genes (DEGs). In upregulated DEGs, the magnitude of changes in expression post-treatment compared to pre-treatment was markedly greater in French bulldogs. Gene set enrichment analysis confirmed that following treatment, French bulldog tumors showed enrichment of key immune-associated pathways previously correlated with poor prognosis. Overall, this study confirmed that French bulldog HGG transcriptomes differ from boxer and Boston terrier transcriptomes, further refining description of the canine glioma transcriptome and providing important information to guide novel therapy development, both for specific dog breeds and for possible correlative variants of human glioblastoma. Full article
(This article belongs to the Special Issue Cancer Immunotherapy Research in Veterinary Medicine)
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11 pages, 2435 KiB  
Article
Protein Expression, Amplification, and Mutation of HER2 Gene in Canine Primary Pulmonary Adenocarcinomas: Preliminary Results
by Barbara Brunetti, Dario de Biase, Francesca Millanta, Luisa Vera Muscatello, Enrico Di Oto, Roberta Marchetti, Ester Lidia Laddaga, Antonio De Leo, Giovanni Tallini and Barbara Bacci
Animals 2024, 14(18), 2625; https://doi.org/10.3390/ani14182625 - 10 Sep 2024
Viewed by 1329
Abstract
Recently, human epidermal growth factor receptor 2 (HER2) has emerged as a therapeutic target of interest for non-small-cell lung cancer in humans. The role of HER2 in canine pulmonary adenocarcinomas is poorly documented. To address this gap, this study employed three methodologies: immunohistochemistry [...] Read more.
Recently, human epidermal growth factor receptor 2 (HER2) has emerged as a therapeutic target of interest for non-small-cell lung cancer in humans. The role of HER2 in canine pulmonary adenocarcinomas is poorly documented. To address this gap, this study employed three methodologies: immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) to investigate the protein expression, gene amplification, and mutation of HER2 in 19 canine primary pulmonary adenocarcinomas. By IHC, 3 out of 19 cases were overexpressed 3+, 6 were 2+, and 10 were negative. With FISH, 2 cases were amplified (12.5%), 3 were inadequate for the analyses, and the others were non-amplified. With NGS, seven cases were inadequate. All other cases were wild-type, except for one IHC 3+ case, which was amplified with FISH and with a specific mutation already described in human pulmonary adenocarcinoma, V659E. This mutation is probably sensitive to tyrosine kinase inhibitory drugs. These results are similar to those in human medicine and to the few data in the literature on canine lung carcinomas; the presence of 12.5% of amplified cases in dogs lays the foundation for future targeted drugs against HER2 alterations. Full article
(This article belongs to the Special Issue Cancer Immunotherapy Research in Veterinary Medicine)
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11 pages, 3869 KiB  
Article
A Preliminary Evaluation of the Prognostic Role of HER-2 and HER-3 Immunohistochemical Expression in Canine Melanomas
by Francesca Parisi, Luigi Aurisicchio, Arianna Pecorari, Alessandro Poli and Francesca Millanta
Animals 2024, 14(10), 1400; https://doi.org/10.3390/ani14101400 - 7 May 2024
Cited by 1 | Viewed by 1204
Abstract
Canine melanoma is a malignant and aggressive neoplasm showing clinical, histological, and molecular features similar to the human counterpart. In human medicine, epidermal growth factor receptors (EGFRs) have already been suggested as prognostic markers and potential therapeutic targets in cutaneous melanoma. The aim [...] Read more.
Canine melanoma is a malignant and aggressive neoplasm showing clinical, histological, and molecular features similar to the human counterpart. In human medicine, epidermal growth factor receptors (EGFRs) have already been suggested as prognostic markers and potential therapeutic targets in cutaneous melanoma. The aim of this study was to evaluate the expression of HER-2 and HER-3 in canine melanomas by immunohistochemistry and correlate their expression to the clinicopathological parameters of the examined tumors. Thirty-seven canine melanoma samples were recruited. Data regarding signalment and clinical parameters were also collected. The population was composed of 18 cutaneous, 16 oral/mucosal, and three digital/foot pad melanomas. Histopathological investigations were carried out to analyze histological type, ulceration, and mitotic count. On each sample, immunohistochemistry was performed using an anti-Melan-A or anti-Melanoma antigen, i.e., anti-HER-2 and anti-HER-3 antibodies. HER-2 and HER-3 positivity were classified using already established scoring criteria and a statistical analysis was carried out. The results highlighted that HER-2 expression was observed in 48.6% of the samples and HER-3 expression in 18.9%. The highest HER 2 score (3+) was recorded in 16.2% of the samples, while the coexpression of the two receptors was detected in 13.5% of the samples. A statistically significant association (p < 0.05) was observed between the expression of HER-2 and HER-3 and the presence of ulceration in oromucosal tumors. This work confirms the expression of HER-2 and HER-3 in canine melanomas and suggests a putative association with negative prognostic parameters. Further studies are necessary to strengthen these data by increasing the samples size and combining pathological examinations with molecular biology in the investigation of EGFR family receptors. Full article
(This article belongs to the Special Issue Cancer Immunotherapy Research in Veterinary Medicine)
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25 pages, 2846 KiB  
Article
Comparison of Nucleosome, Ferritin and LDH Levels in Blood with Clinical Response before and after Electrochemotherapy Combined with IL-12 Gene Electrotransfer for the Treatment of Mast Cell Tumours in Dogs
by Maša Vilfan, Urša Lampreht Tratar, Nina Milevoj, Alenka Nemec Svete, Maja Čemažar, Gregor Serša and Nataša Tozon
Animals 2024, 14(3), 438; https://doi.org/10.3390/ani14030438 - 29 Jan 2024
Viewed by 2157
Abstract
Electrochemotherapy (ECT) in combination with the gene electrotransfer of interleukin 12 (IL-12 GET) has been successfully used in veterinary medicine for the treatment of mast cell tumours (MCT), but the biomarkers that could predict response to this treatment have not yet been investigated. [...] Read more.
Electrochemotherapy (ECT) in combination with the gene electrotransfer of interleukin 12 (IL-12 GET) has been successfully used in veterinary medicine for the treatment of mast cell tumours (MCT), but the biomarkers that could predict response to this treatment have not yet been investigated. The aim of this study was to determine the plasma nucleosome and serum ferritin concentrations, as well as the lactate dehydrogenase (LDH) activity, in the serum of treated patients before and one and six months after treatment to evaluate their utility as potential biomarkers that could predict response to the combined treatment. The study was conducted in 48 patients with a total of 86 MCTs that we treated with the combined treatment. The blood samples used for analysing the potential predictive biomarkers were taken before treatment and one and six months after treatment, when the response to treatment was also assessed. The Nu. Q® Vet Cancer Test, the Canine Ferritin ELISA Kit, and the RX Daytona+ automated biochemical analyser were used to analyse the blood samples. The results showed that the plasma nucleosome concentration (before treatment (BT): 32.84 ng/mL (median); one month after treatment (1 M AT): 58.89 ng/mL (median); p = 0.010) and serum LDH activity (BT: 59.75 U/L (median); 1 M AT: 107.5 U/L (median); p = 0.012) increased significantly one month after treatment and that the increase correlated significantly with the presence of a more pronounced local reaction (necrosis, swelling, etc.) at that time point for both markers (nucleosome: BT (necrosis): 21.61 ng/mL (median); 1 M AT (necrosis): 69.92 ng/mL (median), p = 0.030; LDH: BT (necrosis): 54.75 U/L (median); 1 M AT (necrosis): 100.3 U/L (median), p = 0.048). Therefore, both the plasma nucleosome concentration and serum LDH activity could serve as early indicators of the effect of the treatment. In this context, the serum ferritin concentration showed no significant predictive potential for treatment response (p > 0.999 for all comparisons). In conclusion, this study provides some new and important observations on the use of predictive biomarkers in veterinary oncology. Furthermore, it emphasises the need for the continued identification and validation of potential predictive biomarkers in dogs with MCT and other malignancies undergoing ECT treatment in combination with IL-12 GET to ultimately improve treatment outcomes. Full article
(This article belongs to the Special Issue Cancer Immunotherapy Research in Veterinary Medicine)
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Review

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17 pages, 570 KiB  
Review
Advancing Veterinary Oncology: Next-Generation Diagnostics for Early Cancer Detection and Clinical Implementation
by Aya Hasan Alshammari, Takuya Oshiro, Umbhorn Ungkulpasvich, Junichi Yamaguchi, Masayo Morishita, Sura Abbas Khdair, Hideyuki Hatakeyama, Takaaki Hirotsu and Eric di Luccio
Animals 2025, 15(3), 389; https://doi.org/10.3390/ani15030389 - 30 Jan 2025
Viewed by 424
Abstract
Cancer is a leading cause of death among companion animals, with many cases diagnosed at advanced stages when clinical signs have appeared, and prognosis is poor. Emerging diagnostic technologies, including Artificial Intelligence (AI)-enhanced imaging, liquid biopsies, molecular diagnostics, and nematode-based screening, can improve [...] Read more.
Cancer is a leading cause of death among companion animals, with many cases diagnosed at advanced stages when clinical signs have appeared, and prognosis is poor. Emerging diagnostic technologies, including Artificial Intelligence (AI)-enhanced imaging, liquid biopsies, molecular diagnostics, and nematode-based screening, can improve early detection capabilities in veterinary medicine. These tools offer non-invasive or minimally invasive methods to facilitate earlier detection and treatment planning, addressing the limitations of traditional diagnostics, such as radiography and tissue biopsies. Recent advancements in comparative oncology, which leverage the biological similarities between human and companion animal cancers, underscore their translational value in improving outcomes across species. Technological advances in genomics, bioinformatics, and machine learning are driving a shift toward precision medicine, enabling earlier detection, personalized treatments, and monitoring of disease progression. Liquid biopsy testing detects circulating tumor DNA and tumor cells, providing actionable insights into tumor genetics without invasive procedures. Imaging systems enhance diagnostic precision, offering consistent and accurate tumor identification across veterinary practices, while portable innovations like Caenorhabditis elegans-based screening provide accessible options for underserved regions. As these technologies migrate from human medicine to veterinary applications, they are poised to redefine cancer care for companion animals. This review highlights key advancements in diagnostic technologies and their application in veterinary oncology, with a focus on enhancing early detection, accessibility, and precision in cancer care. By fostering the adoption of these innovations, veterinary oncology can achieve a new standard of care, improving outcomes for both animals and humans through the lens of comparative oncology. Full article
(This article belongs to the Special Issue Cancer Immunotherapy Research in Veterinary Medicine)
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