Pien-Tze-Huang inhibits colorectal cancer liver metastasis in mice by modulating immunosuppressive and fibrotic microenvironments.

Pien-Tze-Huang (PZH) is a well-known traditional Chinese medicine with anti-inflammation and anti-tumor effects. However, its role in tumor metastasis remains largely unknown. In this study, we found that PZH significantly inhibits the liver metastasis of colorectal cancer (CRC) cells in mice. PZH reduces the polarization of macrophages toward the pro-tumor M2 subtype and shifts the immune microenvironment to a tumor-suppressive microenvironment. Moreover, PZH suppresses hepatic stellate cell (HSC) activation and alleviates the fibrotic microenvironment in liver metastatic tissues of mice. We further demonstrated that PZH inhibits the recruitment and M2 polarization of macrophages and the activation of HSCs by decreasing the formation of migrasomes in CRC cells. Our findings suggest that PZH can inhibit liver metastasis of CRC cells in mice by modulating the immune and stromal components of the tumor microenvironment, offering a promising therapeutic strategy for CRC patients with liver metastasis.