Dai Otsubo1, Kimihiro Yamashita2, Mitsugu Fujita3, Masayasu Nishi1, Yutaka Kimura1, Hiroshi Hasegawa1, Satoshi Suzuki1, Yoshihiro Kakeji1. 1. Department of Surgery, Division of Gastrointestinal Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. 2. Department of Surgery, Division of Gastrointestinal Surgery, Kobe University Graduate School of Medicine, Kobe, Japan kiyama@med.kobe-u.ac.jp. 3. Departments of Microbiology and Acute Medicine, Kindai University Graduate School of Medical Sciences, Osaka, Japan.
Abstract
BACKGROUND/AIM: The outcome of patients with malignant tumors is poor if they suffer from lung metastases. Myeloid-derived suppressor cells (MDSCs), a major player for tumor-induced immunosuppression, can be suppressed by certain chemotherapeutic agents, such as low-dose 5-fluorouracil (5-FU) or surgical treatment. Based on these findings, we hypothesized that early-phase treatment by low-dose 5-FU or surgical resection of primary tumors would prevent lung metastasis formation by inhibiting MDSCs. MATERIALS AND METHODS: B16F10 melanoma-bearing C57BL/5 mice with lung metastases were treated with low-dose 5-FU or surgical resection of primary tumors. RESULTS: Low-dose 5-FU chemotherapy inhibited systemic and lung-accumulating MDSCs in tumor-bearing mice. The therapy inhibited lung metastasis formation and prolonged the survival of the animals. Consistently, early-phase resection of primary tumors improved survival, which was concomitant with a reduction of lung-accumulating MDSCs and lung metastases. CONCLUSION: Early-phase treatment may provide therapeutic values to prevent MDSC-mediated lung metastasis formation in tumor-bearing hosts. Copyright
BACKGROUND/AIM: The outcome of patients with malignant tumors is poor if they suffer from lung metastases. Myeloid-derived suppressor cells (MDSCs), a major player for tumor-induced immunosuppression, can be suppressed by certain chemotherapeutic agents, such as low-dose 5-fluorouracil (5-FU) or surgical treatment. Based on these findings, we hypothesized that early-phase treatment by low-dose 5-FU or surgical resection of primary tumors would prevent lung metastasis formation by inhibiting MDSCs. MATERIALS AND METHODS: B16F10 melanoma-bearing C57BL/5 mice with lung metastases were treated with low-dose 5-FU or surgical resection of primary tumors. RESULTS: Low-dose 5-FU chemotherapy inhibited systemic and lung-accumulating MDSCs in tumor-bearing mice. The therapy inhibited lung metastasis formation and prolonged the survival of the animals. Consistently, early-phase resection of primary tumors improved survival, which was concomitant with a reduction of lung-accumulating MDSCs and lung metastases. CONCLUSION: Early-phase treatment may provide therapeutic values to prevent MDSC-mediated lung metastasis formation in tumor-bearing hosts. Copyright
Authors: Zachary Benson; Saeed H Manjili; Mehran Habibi; Georgi Guruli; Amir A Toor; Kyle K Payne; Masoud H Manjili Journal: Biochem Pharmacol Date: 2017-08-10 Impact factor: 5.858
Authors: Tyrel T Smith; Howell F Moffett; Sirkka B Stephan; Cary F Opel; Amy G Dumigan; Xiuyun Jiang; Venu G Pillarisetty; Smitha P S Pillai; K Dane Wittrup; Matthias T Stephan Journal: J Clin Invest Date: 2017-04-24 Impact factor: 14.808