Immune modulation of a lipid-soluble extract of Pinellia pedatisecta Schott in the tumor microenvironment of an HPV + tumor-burdened mouse model.

ETHNOPHARMACOLOGICAL RELEVANCE: Pinellia pedatisecta Schott extract (PE), a traditional Chinese medicine, has been used to reduce swelling, dry dampness and suppress cervical tumors.

AIMS: To evaluate the roles of PE in the regulation of anti-tumor effects and the cellular immune response in the tumor microenvironment.

METHODS: The immune microenvironment of HPV+ TC-1 tumors was examined by immunohistochemistry, real-time PCR and flow cytometry.

RESULTS: Our study demonstrated that PE in vitro could significantly increase the percentage of apoptosis and necrosis in HPV+ TC-1 cells and block the cell cycle phase. In vivo treatment with PE eradicated established subcutaneous HPV+ TC-1 tumors in wild-type C57BL/6 mice by infiltrating CD8+ T cells and CD4+ T cells and by directly suppressing tumor growth and resistance to avascular necrosis. The key factors in the canonical Wnt signaling pathway in the experimental group (PE+mDC+naive CD4+ T cells) were challenged, and the levels of beta-catenin, C-myc, cyclin D1 and PPAR1 were significantly enhanced at the 5th day. In particular, the subset proportion of Th1 cells (characterized by IFNγ production and the transcription factor Tbet) increased significantly, and both Th2 cells (characterized by IL-4 production and the transcription factor GATA3) and Th17 cells (characterized by IL-17 production and the transcription factor RoRγt) decreased profoundly.

CONCLUSIONS: These findings linked the anti-tumor properties of PE with the immune microenvironment to present a reliable basis for the future practical application of PE in cervical cancer as a novel and pharmacologically safe immunotherapy strategy.