Administration of TOC at a dosage of 2.75 mg/kg every other day (EOD) significantly decreased the number of circulating Tregs in dogs with tumors, possibly by immunomodulatory mechanisms, and TOC treatment at a dosage of 2.4‐2.9 mg/kg EOD increased plasma VEGF concentrations, which is consistent with VEGFR inhibition.14, 15 In our study, TOC treatment (dose range, 2.4‐2.9 mg/kg, every Monday, Wednesday, and Friday) also had various modulatory effects in the TME, inhibiting VEGFR2 expression and decreasing the number of tumor‐infiltrating Tregs and HIF‐1α+ tumor cells. This evidence concerns the gene KDR and neoplasm.