Frontiers in immunology
From cold to hot: the immunomodulatory framework of Saikosaponin D in hepatocellular carcinoma therapy
By Huang X, Liu L, Qin M and 1 others.
Abstract
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.
Objective
This review proposes a hypothesis-generating framework for saikosaponin D mediated cold-to-hot immune conversion in hepatocellular carcinoma. We synthesize preclinical evidence and integrate it into a dynamic temporal model to guide future research.