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

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.

Keywords: 5-FU; MDSC; lung metastasis; primary resection; tumor immunity.