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

Autor: Haojun Wang, Quanwei Zhou, Ding Fang Xie, Qingguo Xu, Tongwang Yang, Wei Wang
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cell Death and Disease, Vol 15, Iss 2, Pp 1-14 (2024)
Druh dokumentu: article
ISSN: 2041-4889
DOI: 10.1038/s41419-024-06542-8
Popis: Abstract 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.
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