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

Abstract

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 5^th 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.

Keywords: Cervical cancer; HPV(+) tumor; Helper T (Th) cellular immunity; Pinellia pedatisecta extract (PE); TC-1 cell line.