In hepatocellular carcinoma (HCC), immunotherapy is vital for advanced-stage patients. However, diverse individual responses and tumor heterogeneity have resulted in heterogenous treatment outcomes. Our mechanistic investigations identified LAPTM4B as a crucial gene regulated by ETV1 (a transcription factor), especially in liver cancer stem cells (LCSCs). The influence of LAPTM4B on LCSCs is mediated via the Wnt1/c-Myc/β-catenin pathway. CXCL8 secretion by LAPTM4B drove myeloid-derived suppressor cell (MDSC) migration, inducing unfavorable patient prognosis. LAPTM4B affected PD-L1 receptor expression in tumor microenvironment and enhanced tumor suppression induced by PD-L1 monoclonal antibodies in HCC patients. LAPTM4B up-regulation is correlated with adverse outcomes in HCC patients, sensitizing them to PD-L1 monoclonal antibody therapy.

在肝细胞癌（HCC）中，免疫治疗对于晚期患者至关重要。然而，不同的个体反应和肿瘤异质性导致了不同的治疗结果。我们的机制研究发现 LAPTM4B 是受 ETV1（转录因子）调节的关键基因，尤其是在肝癌干细胞 (LCSC) 中。 LAPTM4B 对 LCSC 的影响是通过 Wnt1/c-Myc/β-连环蛋白途径介导的。 LAPTM4B 分泌的 CXCL8 驱动骨髓源性抑制细胞 (MDSC) 迁移，导致患者预后不良。 LAPTM4B 影响肿瘤微环境中的 PD-L1 受体表达，并增强 HCC 患者中 PD-L1 单克隆抗体诱导的肿瘤抑制。 LAPTM4B 上调与 HCC 患者的不良后果相关，使他们对 PD-L1 单克隆抗体治疗敏感。