China Animal Husbandry & Veterinary Medicine ›› 2025, Vol. 52 ›› Issue (9): 4453-4463.doi: 10.16431/j.cnki.1671-7236.2025.09.040

• Basic Veterinary Medicine • Previous Articles    

Evaluation of 103 Chemotherapy Drugs on Canine T Cell Function and Toxicity

QIN Mengke1,2, LI Huixin1,2, LI Sihao3, ZHANG Qichao4, WANG Rongjun1, MENG Qingda1,2, XIE Shanshan1,2   

  1. 1. College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China;
    2. Research Center for Organoids, College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, China;
    3. Zhengzhou Ruipai Little Playful Animal Hospital, Zhengzhou 450000, China;
    4. Zhengzhou Ruilong Pet Hospital, Zhengzhou 450000, China
  • Received:2025-01-07 Published:2025-08-29

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Abstract: 【Objective】 The purpose of this study was to evaluate the effects of chemotherapeutic drugs on the secretion of interferon-γ (IFN-γ),antitumor function,proliferation and cytotoxicity of T cells derived from peripheral blood of dogs,so as to screen chemotherapeutic drugs with little toxicity and impact on T cell function,in order to use alone or in combination with other immunotherapeutic drugs for the clinical treatment of canine tumor disease. 【Method】 Peripheral blood was collected from healthy dogs,and canine peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation.T cells were cultured and expanded in vitro,and their proportion before and after expansion was verified by flow cytometry.103 chemotherapy drugs were applied to canine T cells at a concentration of 20 μmol/L for 48 h,and the release of IFN-γ was measured by ELISA.Based on the previous experimental data in the laboratory,drugs with anti-tumor activity and a small impact on the secretion of IFN-γ in T cells were selected.After pretreating T cells at a concentration of 20 μmol/L for 12 h,the effect of the drugs on the anti-tumor function of T cells was detected by crystal violet staining,and the toxic effects of the selected chemotherapy drugs on T cells were evaluated in detail through cytotoxicity test and LDH test. 【Result】 Canine peripheral blood T cells were successfully expanded in vitro,reaching 99.70% purity.ELISA results demonstrated that of the 103 drugs tested,14 drugs (13.59%) (including docetaxel) significantly promoted the IFN-γ secretion of T cell (P＜0.05),34 drugs (33.01%) (including brusatol) significantly inhibited the release of IFN-γ (P＜0.05),while 55 drugs (53.40%) (C8-ceramide,etc.) had no statistically significant effect(P＞0.05).Combined with previous experimental data,10 candidate chemotherapy drugs including vinblastine sulfate,C8-ceramide,2'-O-(2-methoxyethyl)-cytidine and docetaxel were identified that preserved IFN-γ production in T cells while maintaining anti-tumor efficacy against canine mammary tumors.Further functional assays confirmed that drugs such as 6-mercaptopurine,docetaxel trihydrate and 2'-O-(2-methoxyethyl)-cytidine did not significantly impair T-cell-mediated antitumor activity.Among them,2'-O-(2-methoxyethyl)-cytidine showed relatively low toxicity to canine T cells,preserving ＞85% proliferation viability while causing no significant cell death. 【Conclusion】 Compounds such as vincristine sulfate,C8-ceramide,2'-O-(2-methoxyethyl)-cytidine and docetaxel had little toxicity on canine T cells.Among them,2'-O-(2-methoxyethyl)-cytidine had low toxicity on T cells and no significant inhibitory effect on their function,and it was expected to become the preferred drug for chemotherapy or combination therapy of canine tumors.

Key words: tumor immunity; canine T lymphocytes; chemotherapy; combination therapy

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