Antrodia cinnamomea Formula Suppresses Prostate Cancer Progression via Immune Modulation and PD-1/PD-L1 Pathway...

Area of Science:

• Integrative Oncology
• Immunotherapy
• Natural Product Chemistry

Background:

• Prostate cancer necessitates novel therapeutic strategies.
• The XIANZHIFANG formula (XZF), a blend of medicinal mushrooms, is explored for its anti-cancer properties.

Purpose of the Study:

• To investigate the therapeutic potential of the XZF formula in prostate cancer.
• To elucidate the mechanisms underlying XZF's anti-cancer effects, including its impact on immune cells and cancer cell lines.

Main Methods:

• High-Performance Liquid Chromatography (HPLC) for chemical profiling of XZF.
• Cytotoxicity assays on non-cancerous and prostate cancer cell lines (PC-3, DU145, LNCaP).
• T-cell activation and immune checkpoint modulation assays (PD-1/PD-L1).
• Macrophage-conditioned medium assays to assess effects on prostate cancer cells.

Main Results:

• XZF contains key triterpenoids and selectively enhances T-cell viability while reducing PD-1 expression on CD8+ T-cells.
• XZF inhibits PD-L1/PD-1 interaction, with complete blockade achieved when combined with atezolizumab.
• XZF exhibits differential antiproliferative effects on prostate cancer cell lines and suppresses their viability and migration via macrophage-conditioned medium.

Conclusions:

• XZF demonstrates multifaceted therapeutic potential against prostate cancer through direct cytotoxicity, immune modulation, and macrophage-mediated suppression.
• The findings support XZF as a promising agent for prostate cancer treatment, particularly in combination with immunotherapies.
• Human macrophage models showed significant inhibitory effects, highlighting potential for clinical translation.