Early-phase Treatment by Low-dose 5-Fluorouracil or Primary Tumor Resection Inhibits MDSC-mediated Lung Metastasis Formation

早期低剂量 5-氟尿嘧啶治疗或原发性肿瘤切除可抑制 MDSC 介导的肺转移形成

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作者:Dai Otsubo, Kimihiro Yamashita, Mitsugu Fujita, Masayasu Nishi, Yutaka Kimura, Hiroshi Hasegawa, Satoshi Suzuki, Yoshihiro Kakeji

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

Conclusion

Early-phase treatment may provide therapeutic values to prevent MDSC-mediated lung metastasis formation in tumor-bearing hosts.

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.

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