Introduction

Arginase expression by myeloid-derived suppressor cells (MDSCs) is known to inhibit T lymphocyte functions in humans and mice with cancer. The objectives of this study were to determine the effect of arginase on canine lymphocyte cytotoxicity and proliferation, and to evaluate the effect of vincristine chemotherapy on blood MDSC prevalence and arginase expression in dogs with lymphoma.

Methods

Peripheral blood mononuclear cells (PBMCs) isolated from cancer-bearing dogs were exposed to increasing concentrations of arginase (0–100 nM) in the presence or absence of concanavalin A (5 μg/ml). After 2 days, flow cytometry was performed to evaluate changes in CD3, CD4, CD8, CD45RA, CD62L, granzyme B, CD25, and Ki67 expression on lymphocytes. Additionally, PBMCs were collected from dogs with naïve, multicentric, high-grade lymphoma prior to, and one week post, vincristine chemotherapy (without concurrent prednisone). Response to vincristine was prospectively assessed. The proportion of MDSCs (CD11b+CD14-MHCII-) and MDSC expression of arginase was measured by flow cytometry.

Results

Arginase decreased expression of granzyme B on CD8+ T lymphocytes, and inhibited CD4+ and CD8+ T lymphocyte proliferation. Replicates of these experiments are pending. Vincristine chemotherapy induced a decrease in the percentage of MDSCs in 3 of 4 dogs and decreased arginase expression in MDSCs of all 4 dogs. Analysis of additional samples and correlation with response is still underway.

Conclusion

These preliminary results suggest vincristine chemotherapy, or reduction in lymphoma burden, may lead to a decreased prevalence of circulating MDSCs and reduction of their arginase expression, which may alleviate T lymphocyte suppression in these dogs.

Funding Information

Research reported in this abstract was supported by the LSU Department of Veterinary Clinical Sciences Competitive Research Program.