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Immunotherapy against programmed death-1/programmed death ligand 1 in hepatocellular carcinoma: Importance of molecular variations, cellular heterogeneity, and cancer stem cells

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摘要 Hepatocellular carcinoma(HCC)is a heterogeneous malignancy related to diverse etiological factors.Different oncogenic mechanisms and genetic variations lead to multiple HCC molecular classifications.Recently,an immune-based strategy using immune checkpoint inhibitors(ICIs)was presented in HCC therapy,especially with ICIs against the programmed death-1(PD-1)and its ligand PD-L1.However,despite the success of anti-PD-1/PD-L1 in other cancers,a substantial proportion of HCC patients fail to respond.In this review,we gather current information on biomarkers of anti-PD-1/PD-L1 treatment and the contribution of HCC heterogeneity and hepatic cancer stem cells(CSCs).Genetic variations of PD-1 and PD-L1 are associated with chronic liver disease and progression to cancer.PD-L1 expression in tumoral tissues is differentially expressed in CSCs,particularly in those with a close association with the tumor microenvironment.This information will be beneficial for the selection of patients and the management of the ICIs against PD-1/PD-L1.
出处 《World Journal of Stem Cells》 SCIE 2021年第7期795-824,共30页 世界干细胞杂志(英文版)(电子版)
基金 Supported by 2020 Grant of the Fondazione Umberto Veronesi,Milan,Italy(to Sukowati CHC) a Grant of the Regione Autonomo Friuli Venezia Giulia in Progetti Internazionali 2020(DGR 2195 dd 20/12/2019)to the FIF.
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