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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Frontiers Media S.A.
2021
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oai:doaj.org-article:0cfee634520c4c68a85e229019c24a1f2021-12-02T08:21:22ZT Cell Immune Profiles of Blood and Tumor in Dogs Diagnosed With Malignant Melanoma2297-176910.3389/fvets.2021.772932https://doaj.org/article/0cfee634520c4c68a85e229019c24a1f2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fvets.2021.772932/fullhttps://doaj.org/toc/2297-1769Investigation 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.Ellen E. SpargerHong ChangNing ChinRobert B. RebhunSita S. WithersHung KieuRobert J. CanterArta M. MonjazebMichael S. KentFrontiers Media S.A.articlemelanomacaninedogimmune profileone healthcomparative oncologyVeterinary medicineSF600-1100ENFrontiers in Veterinary Science, Vol 8 (2021) |
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melanoma canine dog immune profile one health comparative oncology Veterinary medicine SF600-1100 |
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melanoma canine dog immune profile one health comparative oncology Veterinary medicine SF600-1100 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 |
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. |
format |
article |
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 |
title |
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_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_sort |
t cell immune profiles of blood and tumor in dogs diagnosed with malignant melanoma |
publisher |
Frontiers Media S.A. |
publishDate |
2021 |
url |
https://doaj.org/article/0cfee634520c4c68a85e229019c24a1f |
work_keys_str_mv |
AT ellenesparger tcellimmuneprofilesofbloodandtumorindogsdiagnosedwithmalignantmelanoma AT hongchang tcellimmuneprofilesofbloodandtumorindogsdiagnosedwithmalignantmelanoma AT ningchin tcellimmuneprofilesofbloodandtumorindogsdiagnosedwithmalignantmelanoma AT robertbrebhun tcellimmuneprofilesofbloodandtumorindogsdiagnosedwithmalignantmelanoma AT sitaswithers tcellimmuneprofilesofbloodandtumorindogsdiagnosedwithmalignantmelanoma AT hungkieu tcellimmuneprofilesofbloodandtumorindogsdiagnosedwithmalignantmelanoma AT robertjcanter tcellimmuneprofilesofbloodandtumorindogsdiagnosedwithmalignantmelanoma AT artammonjazeb tcellimmuneprofilesofbloodandtumorindogsdiagnosedwithmalignantmelanoma AT michaelskent tcellimmuneprofilesofbloodandtumorindogsdiagnosedwithmalignantmelanoma |
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1718398526039261184 |