T Cell Immune Profiles of Blood and Tumor in Dogs Diagnosed With Malignant Melanoma

Authors

Ellen E. Sparger, Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
Hong Chang, Center for Companion Animal Health, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
Ning Chin, California National Primate Research Center, Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA, United States.
Robert B. Rebhun, Center for Companion Animal Health, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
Sita S. Withers, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, United States.
Hung Kieu, Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
Robert J. Canter, Surgical Oncology, School of Medicine, University of California, Davis, Sacramento, CA, United States.
Arta M. Monjazeb, Radiation Oncology, School of Medicine, University of California, Davis, Sacramento, CA, United States.
Michael S. Kent, Center for Companion Animal Health, Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.

Document Type

Article

Publication Date

1-1-2021

Abstract

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 ( = 11-20) T cell phenotypes with healthy controls dogs ( = 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 ( = 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.

Publication Source (Journal or Book title)

Frontiers in veterinary science

First Page

772932

Recommended Citation

Sparger, E. E., Chang, H., Chin, N., Rebhun, R. B., Withers, S. S., Kieu, H., Canter, R. J., Monjazeb, A. M., & Kent, M. S. (2021). T Cell Immune Profiles of Blood and Tumor in Dogs Diagnosed With Malignant Melanoma. Frontiers in veterinary science, 8, 772932. https://doi.org/10.3389/fvets.2021.772932