From cold to hot: the immunomodulatory framework of Saikosaponin D in hepatocellular carcinoma therapy

Background

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related mortality worldwide. Despite the clinical success of immune checkpoint inhibitors, a substantial proportion of patients exhibit primary resistance, largely attributable to the immunosuppressive "cold" tumor microenvironment (TME). Saikosaponin D (SSd), a triterpenoid saponin derived from Bupleurum falcatum L., has emerged as a multifaceted immunomodulator with potential to remodel the TME, yet its role in converting "cold" HCC to an immunologically responsive "hot" phenotype remains systematically unexplored.