Early-phase Treatment by Low-dose 5-Fluorouracil or Primary Tumor Resection Inhibits MDSC-mediated Lung Metastasis Formation.
Early-phase Treatment by Low-dose 5-Fluorouracil or Primary Tumor Resection Inhibits MDSC-mediated Lung Metastasis Formation.
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发表时间：
2015-08
影响因子：
2
通讯作者：
Dai Otsubo;K. Yamashita;M. Fujita;Masayasu Nishi;Y. Kimura;H. Hasegawa;Satoshi Suzuki;Y. Kakeji
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文献类型：
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作者：
Dai Otsubo;K. Yamashita;M. Fujita;Masayasu Nishi;Y. Kimura;H. Hasegawa;Satoshi Suzuki;Y. Kakeji
背景/目的恶性肿瘤患者发生肺转移后预后较差。髓源性抑制细胞（MDSCs）是肿瘤诱导免疫抑制的主要参与者，可被某些化疗药物抑制，如低剂量5-氟尿嘧啶（5-FU）或手术治疗。基于这些发现，我们假设早期低剂量5-FU治疗或手术切除原发肿瘤可以通过抑制MDSCs来阻止肺转移的形成。材料与方法B16F10黑素瘤C57BL/5小鼠肺转移灶低剂量5- fu治疗或手术切除原发肿瘤。结果低剂量5-FU化疗抑制荷瘤小鼠全身和肺部积聚的MDSCs。该疗法抑制了肺转移的形成，延长了动物的生存期。一致地，早期切除原发肿瘤可以提高生存率，这伴随着肺部积聚的MDSCs和肺转移的减少。结论早期治疗对预防mdsc介导的荷瘤细胞肺转移具有一定的治疗价值。
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.