Wang Wei-Kuang, Lu Meng-Fan, Kuan Yu-Diao, Lee Che-Hsin
Department of Environmental Engineering and Science, Feng Chia University Taichung 40407, Taiwan.
Department of Environmental Engineering and Science, Feng Chia University Taichung 40407, Taiwan ; Graduate Institute of Basic Medical Science, School of Medicine, China Medical University Taichung 40404, Taiwan.
Am J Cancer Res. 2015 Jun 15;5(7):2222-8. eCollection 2015.
Systemic administration of Salmonella to tumor-bearing mice leads to its preferential accumulation in tumor sites, the enhancement of host immunity, and the inhibition of tumor growth. However, the underlying mechanism for Salmonella-induced antitumor immune response via oral delivery remained uncertain. Herein, we used mouse colorectal cancer (CT26) as tumor model to study the therapeutic effects after oral delivery of Salmonella. When orally administered into tumor-bearing mice, Salmonella significantly accumulated in the tumor sites, inhibited tumor growth and extended the survival of mice. No obvious toxicity was observed during orally administered Salmonella by examining body weight and inflammatory cytokines. As indoleamine 2, 3-dioxygenase 1 (IDO) is a crucial mediator for tumor-mediated immune tolerance, we examined the expression of IDO. We demonstrated that Salmonella inhibited IDO expression in mouse cancer cells. Furthermore, immunohistochemical studies of the tumors revealed the infiltration of neutrophils and T cells in mice treated with Salmonella. In conclusion, our results indicate that Salmonella exerts its tumoricidal effects and stimulates T cell activities by inhibiting IDO expression. Oral delivery of Salmonella may, represent a potential strategy for the treatment of tumor.
给荷瘤小鼠进行全身性沙门氏菌给药会导致其在肿瘤部位优先蓄积、增强宿主免疫力并抑制肿瘤生长。然而，经口服给药的沙门氏菌诱导抗肿瘤免疫反应的潜在机制仍不明确。在此，我们使用小鼠结直肠癌（CT26）作为肿瘤模型来研究口服沙门氏菌后的治疗效果。当给荷瘤小鼠口服给药时，沙门氏菌在肿瘤部位显著蓄积，抑制肿瘤生长并延长小鼠存活时间。通过检查体重和炎性细胞因子，在口服沙门氏菌期间未观察到明显毒性。由于吲哚胺2,3-双加氧酶1（IDO）是肿瘤介导的免疫耐受的关键介质，我们检测了IDO的表达。我们证明沙门氏菌抑制小鼠癌细胞中IDO的表达。此外，对肿瘤的免疫组化研究显示，经沙门氏菌治疗的小鼠中有中性粒细胞和T细胞浸润。总之，我们的结果表明，沙门氏菌通过抑制IDO表达发挥其杀瘤作用并刺激T细胞活性。口服沙门氏菌可能代表一种治疗肿瘤的潜在策略。
