Flow Cytometric Analysis of Peripheral Blood and Tumor-Infiltrating Regulatory T Cells in Dogs with Oral Malignant Melanoma

Tominaga, Mitsuhiro; Horiuchi, Yutaka; Ichikawa, Mika; Yamashita, Masao; Okano, Kumiko; Jikumaru, Yuri; Nariai, Yoko; Kadosawa, Tsuyoshi

doi:10.1177/104063871002200317

Cited by 49 publications

(67 citation statements)

References 16 publications

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“…However, it is possible that other T-cell parameters, such as vaccine-elicited T-cell phenotype, the ability to release other cytokines and the presence of cells negatively regulating the immune response, may have an impact. The immunosuppressive microenvironment at the tumor site and draining LN (48,49) may have locally inhibited the vaccine-induced immune response, allowing local recurrences and/or metastasis to other satellite LN to occur in some dogs.…”

Section: Discussionmentioning

confidence: 99%

CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

Riccardo¹,

Iussich

Maniscalco

et al. 2014

Clinical Cancer Research

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Purpose: Due to the many similarities with its human counterpart, canine malignant melanoma (cMM) is a valuable model in which to assess the efficacy of novel therapeutic strategies. The model is herein used to evaluate the immunogenicity, safety, and therapeutic efficacy of a human chondroitin sulfate proteoglycan-4 (hCSPG4) DNA-based vaccine. The fact that homology between hCSPG4 and cCSPG4 amino-acidic sequences stands at more than 80% provides the rationale for using an hCSPG4 DNA vaccine in the cMM model.Experimental Design: Dogs with stage II-III surgically resected CSPG4-positive oral MM were subjected to monthly intramuscular plasmid administration, which was followed immediately by electroporation (electrovaccination) for at least 6, and up to 20, months. The immunogenicity, safety, and therapeutic efficacy of the vaccine have been evaluated.Results: hCSPG4 electrovaccination caused no clinically relevant local or systemic side effects and resulted in significantly longer overall and disease-free survival times in 14 vaccinated dogs as compared with 13 nonvaccinated controls. All vaccinated dogs developed antibodies against both hCSPG4 and cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T-cell response and only two gave a detectable interferon (IFN)g response.Conclusion: Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the "self" antigen and seems to be effective in treating cMM, laying the foundation for its translation to a human clinical setting.

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Section: Discussionmentioning

confidence: 99%

CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

Riccardo¹,

Iussich

Maniscalco

et al. 2014

Clinical Cancer Research

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“…Specifically, some studies have focused their investigations on dogs with tumors. [4][5][6]11,15,17 It has been described that tumor-bearing dogs have a higher number of leukocytes than normal dogs. 6 Absolute cell and relative percentage of cluster of differentiation (CD)3+ T cells, CD4+ T helper (Th) cells, CD8+ T cytotoxic (Tc) cells, and CD21+ B cells in dogs with tumors are notably decreased in comparison with healthy dogs.…”

mentioning

confidence: 99%

“…4,5 An increased population of regulatory T cells has also been reported in dogs with various cancers. 5,11,15 Despite extensive research in human beings, few reports evaluating the role of different peripheral lymphocyte subsets in dogs with non-oncologic diseases are available. In the present study, the immunophenotype found in the peripheral blood lymphocytes of dogs with several different pathologic conditions is evaluated.…”

mentioning

confidence: 99%

Comparative study of peripheral blood leukocytes in healthy dogs and in dogs with cancer and inflammatory diseases

et al. 2014

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Abstract. In the present study, the peripheral blood lymphocyte subset distribution was compared between healthy dogs and dogs with chronic gastrointestinal disease, dental and skin conditions, and cancer. The immunophenotype of the group with chronic gastrointestinal disease and the group with dental and skin conditions showed no statistically significant differences with other groups of healthy or diseased dogs. When compared with healthy dogs, animals with cancer showed significantly lower absolute values of T cytotoxic cells (CD3+, CD8+) and lymphocytes that express major histocompatibility complex (MHC) class II (MHC-II+) in peripheral blood. The results suggest that peripheral blood immunophenotype is mainly altered in dogs with cancer but not in other diseases. Further studies are required to evaluate the clinical relevance of these findings.

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“…51 In these reports, dogs with all tumors studied (oral melanoma, osteosarcoma, mast cell tumor, lymphoma, and soft tissue sarcoma) showed significantly higher Treg percentages when compared to healthy animals. 3,51,81 Moreover, in oral melanomas, the percentages of Tregs were significantly increased in the tumor site when compared to peripheral blood of the same animal. The authors hypothesized that tumor cells induced either local proliferation or selective migration of Tregs to tumor-infiltrated sites.…”

Section: Tregs and Cancermentioning

confidence: 98%

Regulatory T Cells and Their Role in Animal Disease

Veiga-Parga

2016

Vet Pathol

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In humans and mouse models, Foxp3 þ regulatory T cells are known to control all aspects of immune responses. However, only limited information exists on these cells' role in diseases of other animals. In this review, we cover the most important features and different types of regulatory T cells, which include those that are thymus-derived and peripherally induced, the mechanisms by which they control immune responses by targeting effector T cells and antigen-presenting cells, and most important, their role in animal health and diseases including cancer, infections, and other conditions such as hypersensitivities and autoimmunity. Although the literature regarding regulatory T cells in domestic animal species is still limited, multiple articles have recently emerged and are discussed. Moreover, we also discuss the evidence suggesting that regulatory T cells might limit the magnitude of effector responses, which can have either a positive or negative result, depending on the context of animal and human disease. In addition, the issue of plasticity is discussed because plasticity in regulatory T cells can result in the loss of their protective function in some microenvironments during disease. Lastly, the manipulation of regulatory T cells is discussed in assessing the possibility of their use as a treatment in the future.

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Flow Cytometric Analysis of Peripheral Blood and Tumor-Infiltrating Regulatory T Cells in Dogs with Oral Malignant Melanoma

Cited by 49 publications

References 16 publications

CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

Comparative study of peripheral blood leukocytes in healthy dogs and in dogs with cancer and inflammatory diseases

Regulatory T Cells and Their Role in Animal Disease

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