LAPTM4B-mediated hepatocellular carcinoma stem cell proliferation and MDSC migration: implications for HCC progression and sensitivity to PD-L1 monoclonal antibody therapy

Cell Death Dis. 2024 Feb 22;15(2):165. doi: 10.1038/s41419-024-06542-8.


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.

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • B7-H1 Antigen / genetics
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / therapy
  • Cell Proliferation
  • Humans
  • Immunotherapy / methods
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / therapy
  • Membrane Proteins / metabolism
  • Myeloid-Derived Suppressor Cells* / metabolism
  • Oncogene Proteins / metabolism
  • Transcription Factors
  • Tumor Microenvironment


  • B7-H1 Antigen
  • Antibodies, Monoclonal
  • Transcription Factors
  • LAPTM4B protein, human
  • Membrane Proteins
  • Oncogene Proteins