Feiyanning downregulating CXCLs/CXCR2 axis to suppress TANs infiltration in the prevention of lung cancer metastasis

Ethnopharmacological relevance: Tumor-associated neutrophils (TANs) play an important role in tumor metastasis. The Traditional Chinese medicine (TCM) Feiyanning (Fyn) has been clinically proven to effectively prevent the recurrence and metastasis of lung Cancer, improve immunity, and prolong the survival period of lung Cancer patients. However, its anti-metastatic immune mechanism has not been fully elucidated. To this end, we studied the mechanism of FYN's regulation of neutrophils infiltration in the tumor microenvironment (TME).

Aim of the study: To explore the anti-metastatic mechanism of Fyn from the perspective of anti-immunosuppressive phenotype neutrophils infiltration in the TME.

Materials and methods: TCM network pharmacological analysis was used to predict Feiyanning effective target. Flow cytometry was used to detect the proportion of immune cell subsets in the TME. Lung metastases were investigated in C57 mice by tail vein injection. Protein expression was evaluated by immunohistochemistry and Western blot. Gene expression was evaluated by qRT-PCR.

Results: Fyn could reshape the tumor immune microenvironment. It prevents Tregs, M2 macrophages, and neutrophils infiltration, as well as recruits T cells, NK cells, and DCs, and improves DCs activation. In addition, Fyn could regulate the polarization of TANs, inhibit the infiltration of neutrophils with an immunosuppressive phenotype, downregulate CXCLs/CXCR2 axis and inhibitory factors like Arg-1 and TGF-β, and up-regulate the immune effector molecule ICAM-1. Furthermore, Fyn increases anti-tumor immune effects in the TME to prevent tumor cells from spreading to the lungs.

Conclusion: This study clarifies the potential mechanism of Fyn in regulating neutrophils infiltration and anti-metastasis. Fyn may regulate neutrophils infiltration in the TME by regulating CXCLs/CXCR2 axis.