Recombinant Newcastle disease virus expressing human IFN-λ1 (rL-hIFN-λ1) inhibits lung cancer migration through repolarizating macrophage from M2 to M1 phenotype

BACKGROUND: Tumor-associated macrophages (TAMs) are frequently infiltrated in tumor microenvironment and promote tumor progression. Lung cancer development largely depends upon the essential contributions from the TAMs which generally polarize into M2 TAMs and produce abundant anti-inflammatory factors and facilitate tumor development. The recombinant Newcastle disease virus expressing human IFN-λ1 (rL-hIFN-λ1) could regulate Th1/Th2 immune response to produce anti-tumor microenvironment. However, the interaction between rL-hIFN-λ1 and macrophages polarization remains unclear. METHODS: The THP-1 cells were used to construct the THP-1-M0, THP-1-M1, THP-1-M2 and THP-1-rL-hIFN-λ1 macrophage models. qRT-PCR and Immunofluorescence were used to detect the polarization phenotype of macrophage polarized by rL-hIFN-λ1. The inhibitory properties of THP-rL-hIFN-λ1 on A549 cells and H446 cells were determined by a Clonogenic assay, as well as scratch migration assays and Transwell were used to explore the capability of migration. Furthermore, the M1/M2 infiltration density in different clinical stages of lung cancer tissues were examined. RESULTS: It was showed that rL-hIFN-λ1 could induce normal macrophages to differentiate into THP-1-M1 macrophages. Meanwhile, rL-hIFN-λ1 could also direct THP-1-M2 macrophages polarization into THP-1-M1 macrophages. Supernatants from rL-hIFN-λl induced macrophages inhibited colony formation, migration and invasion of lung cancer cells in vitro which was similar to THP-1-M1 macrophages. Moreover, analysis of clinical tumor tissues indicated that M1-type macrophages decreased gradually with the development of the clinical stage of lung cancer. CONCLUSIONS: Therefore, rL-hIFN-λl induced significant suppression of primary lung tumor growth and spontaneous lung metastases through regulating macrophages function, and it was expected to become a new biological therapy for lung cancer.