Foxp3Regulatory T Cells Associated With CCL17/CCR4 Expression in Carcinomas of Dogs.

Abstract

Regulatory T cells (Tregs) can be targeted in cancer immunotherapy. A previous study has shown that the chemokine CCL17 and the receptor CCR4 play a role in Treg recruitment in canine urothelial carcinoma. Here, we describe the association of tumor-infiltrating Tregs with CCL17/CCR4 expression in dogs with other carcinomas. In this study, we investigated 23 dogs with mammary carcinoma, 14 dogs with oral squamous cell carcinoma, 16 dogs with pulmonary adenocarcinoma, and 8 healthy control dogs. Immunohistochemistry showed that Foxp3Tregs and CCR4cells were increased in the tumor tissues of mammary carcinoma, squamous cell carcinoma, and pulmonary adenocarcinoma, when compared with the healthy tissues. The number of CCR4cells was associated with that of Foxp3Tregs. Double immunofluorescence labeling confirmed that most tumor-infiltrating Foxp3Tregs expressed CCR4. In vitro, canine carcinoma cell lines expressedmRNA. Quantitative RT-PCR (reverse transcriptase-polymerase chain reaction) showed thatmRNA expression in canine carcinomas was increased approximately 10- to 25-fold relative to that of healthy tissues. These results suggest that the CCL17/CCR4 axis may drive Treg recruitment in a variety of canine carcinomas. CCR4 blockade may be a potential therapeutic option for tumor eradication through Treg depletion.