T Cell Immune Profiles of Blood and Tumor in Dogs Diagnosed With Malignant Melanoma
Investigation of canine T cell immunophenotypes in canine melanomas as prognostic biomarkers for disease progression or predictive biomarkers for targeted immunotherapeutics remains in preliminary stages. We aimed to examine T cell phenotypes and function in peripheral blood mononuclear cells (PBMC)...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Veterinary Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2021.772932/full |
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| author | Ellen E. Sparger Hong Chang Ning Chin Robert B. Rebhun Sita S. Withers Hung Kieu Robert J. Canter Arta M. Monjazeb Michael S. Kent |
| author_facet | Ellen E. Sparger Hong Chang Ning Chin Robert B. Rebhun Sita S. Withers Hung Kieu Robert J. Canter Arta M. Monjazeb Michael S. Kent |
| author_sort | Ellen E. Sparger |
| collection | DOAJ |
| description | Investigation of canine T cell immunophenotypes in canine melanomas as prognostic biomarkers for disease progression or predictive biomarkers for targeted immunotherapeutics remains in preliminary stages. We aimed to examine T cell phenotypes and function in peripheral blood mononuclear cells (PBMC) and baseline tumor samples by flow cytometry, and to compare patient (n = 11–20) T cell phenotypes with healthy controls dogs (n = 10–20). CD3, CD4, CD8, CD25, FoxP3, Ki67, granzyme B, and interferon-γ (IFN-γ) were used to classify T cell subsets in resting and mitogen stimulated PBMCs. In a separate patient cohort (n = 11), T cells were classified using CD3, CD4, CD8, FoxP3, and granzyme B in paired PBMC and single cell suspensions of tumor samples. Analysis of flow cytometric data of individual T cell phenotypes in PBMC revealed specific T cell phenotypes including FoxP3+ and CD25+FoxP3- populations that distinguished patients from healthy controls. Frequencies of IFN-γ+ cells after ConA stimulation identified two different patient phenotypic responses, including a normal/exaggerated IFN-γ response and a lower response suggesting dysfunction. Principle component analysis of selected T cell immunophenotypes also distinguished patients and controls for T cell phenotype and revealed a clustering of patients based on metastasis detected at diagnosis. Findings supported the overall hypothesis that canine melanoma patients display a T cell immunophenotype profile that is unique from healthy pet dogs and will guide future studies designed with larger patient cohorts necessary to further characterize prognostic T cell immunophenotypes. |
| first_indexed | 2024-12-14T13:45:52Z |
| format | Article |
| id | doaj.art-0cfee634520c4c68a85e229019c24a1f |
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| issn | 2297-1769 |
| language | English |
| last_indexed | 2024-12-14T13:45:52Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Veterinary Science |
| spelling | doaj.art-0cfee634520c4c68a85e229019c24a1f2022-12-21T22:59:19ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692021-12-01810.3389/fvets.2021.772932772932T Cell Immune Profiles of Blood and Tumor in Dogs Diagnosed With Malignant MelanomaEllen E. Sparger0Hong Chang1Ning Chin2Robert B. Rebhun3Sita S. Withers4Hung Kieu5Robert J. Canter6Arta M. Monjazeb7Michael S. Kent8Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United StatesCenter for Companion Animal Health, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, United StatesCalifornia National Primate Research Center, Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA, United StatesCenter for Companion Animal Health, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, United StatesDepartment of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, United StatesDepartment of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United StatesSurgical Oncology, School of Medicine, University of California, Davis, Sacramento, CA, United StatesRadiation Oncology, School of Medicine, University of California, Davis, Sacramento, CA, United StatesCenter for Companion Animal Health, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, United StatesInvestigation of canine T cell immunophenotypes in canine melanomas as prognostic biomarkers for disease progression or predictive biomarkers for targeted immunotherapeutics remains in preliminary stages. We aimed to examine T cell phenotypes and function in peripheral blood mononuclear cells (PBMC) and baseline tumor samples by flow cytometry, and to compare patient (n = 11–20) T cell phenotypes with healthy controls dogs (n = 10–20). CD3, CD4, CD8, CD25, FoxP3, Ki67, granzyme B, and interferon-γ (IFN-γ) were used to classify T cell subsets in resting and mitogen stimulated PBMCs. In a separate patient cohort (n = 11), T cells were classified using CD3, CD4, CD8, FoxP3, and granzyme B in paired PBMC and single cell suspensions of tumor samples. Analysis of flow cytometric data of individual T cell phenotypes in PBMC revealed specific T cell phenotypes including FoxP3+ and CD25+FoxP3- populations that distinguished patients from healthy controls. Frequencies of IFN-γ+ cells after ConA stimulation identified two different patient phenotypic responses, including a normal/exaggerated IFN-γ response and a lower response suggesting dysfunction. Principle component analysis of selected T cell immunophenotypes also distinguished patients and controls for T cell phenotype and revealed a clustering of patients based on metastasis detected at diagnosis. Findings supported the overall hypothesis that canine melanoma patients display a T cell immunophenotype profile that is unique from healthy pet dogs and will guide future studies designed with larger patient cohorts necessary to further characterize prognostic T cell immunophenotypes.https://www.frontiersin.org/articles/10.3389/fvets.2021.772932/fullmelanomacaninedogimmune profileone healthcomparative oncology |
| spellingShingle | Ellen E. Sparger Hong Chang Ning Chin Robert B. Rebhun Sita S. Withers Hung Kieu Robert J. Canter Arta M. Monjazeb Michael S. Kent T Cell Immune Profiles of Blood and Tumor in Dogs Diagnosed With Malignant Melanoma Frontiers in Veterinary Science melanoma canine dog immune profile one health comparative oncology |
| title | T Cell Immune Profiles of Blood and Tumor in Dogs Diagnosed With Malignant Melanoma |
| title_full | T Cell Immune Profiles of Blood and Tumor in Dogs Diagnosed With Malignant Melanoma |
| title_fullStr | T Cell Immune Profiles of Blood and Tumor in Dogs Diagnosed With Malignant Melanoma |
| title_full_unstemmed | T Cell Immune Profiles of Blood and Tumor in Dogs Diagnosed With Malignant Melanoma |
| title_short | T Cell Immune Profiles of Blood and Tumor in Dogs Diagnosed With Malignant Melanoma |
| title_sort | t cell immune profiles of blood and tumor in dogs diagnosed with malignant melanoma |
| topic | melanoma canine dog immune profile one health comparative oncology |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2021.772932/full |
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