Immune checkpoint inhibitors in HCC: Cellular, molecular and systemic data

Harkus, Uasim; Wankell, Miriam; Palamuthusingam, Pranavan; McFarlane, Craig; Hebbard, Lionel

doi:10.1016/j.semcancer.2022.01.005

Cited by 47 publications

(34 citation statements)

References 224 publications

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“…Molecular targeted drugs with higher selectivity, sensitivity, and effectiveness have become the first-line drugs for HCC treatment. However, the problems of targeted therapy, such as severe side effects, low survival rate, and drug resistance, have yet to be resolved [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing

et al. 2022

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Section: Introductionmentioning

confidence: 99%

Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing

et al. 2022

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“…With the characteristics of high malignancy and rapid progress, more than half of patients with HCC were diagnosed at a late stage with a worse clinical outcome and would die within 3-6 months after diagnosis, which mainly resulted from tumor location, tumor cell invasion, and metastasis, tumor recurrence, and body characteristics, although significant advances have been achieved in the medical fields of anticancer therapeutics [1,[24][25][26]. Various genetic variations have a role in the start and progression of HCC.…”

Section: Discussionmentioning

confidence: 99%

“…Author details 1 Department of Blood transfusion, Zhengzhou University First Affiliated Hospital, Zhengzhou, China. 2 Department of Medical Laboratory, Zhengzhou University First Affiliated Hospital, Zhengzhou, China.…”

Section: Abbreviationsmentioning

confidence: 99%

“…Hepatocellular carcinoma (HCC), which accounts for almost 90% of all primary liver cancers, is one of the most frequent tumors and the leading cause of cancer-related deaths in the world [1]. The incidence and development of HBV or HCV infection, alcohol abuse, HIV co-infection, cirrhosis, and aflatoxin exposure may vary depending on the prevalence of risk factors such as HBV or HCV infection, alcohol abuse, HIV co-infection, cirrhosis, and aflatoxin exposure [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

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Identification of HM13 as a prognostic indicator and a predictive biomarker for immunotherapy in hepatocellular carcinoma

Zhang

Yang

et al. 2022

BMC Cancer

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Background Histocompatibility minor 13 (HM13) is a signal sequence stubbed intramembrane cleavage catalytic protein that is essential for cell signaling, intracellular communication, and cancer. However, the expression of HM13 and its prognostic value, association with tumor-infiltrating immune cells (TIICs) in the microenvironment, and potential to predict immunotherapeutic response in HCC are unknown. Methods The HM13 expression, clinicopathology analysis, and its influence on survival were analyzed in multiple public databases and further verified in collected HCC and normal tissues by qRT-PCR and immunohistochemistry staining assay (IHC). Furthermore, the lentivirus vector encoding HM13-shRNA to manipulate HM13 expression was selected to investigate whether HM13 could influence the malignant growth and metastasis potential of HCC cells. Finally, significant impacts of HM13 on the HCC tumor microenvironment (TME) and reaction to immune checkpoint inhibitors were analyzed. Results Upregulated HM13 was substantially correlated with poor prognosis in patients with HCC, and could facilitate the proliferation and migratory potential of HCC cells. Additionally, patients with high HM13 expression might be more sensitive to immunotherapy. Conclusions HM13 might be a prognostic biomarker and potential molecular therapeutic target for HCC.

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“…1,2 The incidence of HCC is more prevalent in patients with chronic liver disease, such as chronic hepatitis (B and C), liver cirrhosis, fatty liver disease, exposure to aflatoxin, and excess consumption of alcohol. [3][4][5][6] Medical treatments such as chemotherapy, chemoembolization, ablation, and proton beam therapy have been ineffective for these patients and the majority of them show disease recurrence, rapid progression, and metastases. 7,8 Despite various advancements, pharmacological therapy has had a limited therapeutic impact.…”

Section: Introductionmentioning

confidence: 99%

Sorafenib-Entrapped, Self-Assembled Pullulan–Stearic Acid Biopolymer-Derived Drug Delivery System to PLC/PRF/5 Hepatocellular Carcinoma Model

Chirayil¹,

Kumar²

2022

IJN

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This study aimed to design a prototypic drug delivery system (DDS) made of an amphiphilic, pullulan (Pull)-derived biodegradable polymer for targeting the asialoglycoprotein receptor (ASGPR) overexpressed in HCC. Stearic acid (SA) was conjugated to increase the hydrophobicity of pullulan (Pull-SA). Methods: Pullulan (Pull) was linked to stearic acid (SA) after functional group modifications via EDC/NHS chemistry and characterized. Sorafenib tosylate (SRFT) was entrapped in pullulan-stearic acid nanoparticles (Pull-SA-SRFT) and its particle size, zeta potential, entrapment efficiency (EE), loading capacity (LC), and release efficiency was measured. The competence of Pull-SA-SRFT over SRFT in vitro was assessed using the ASGPR over-expressing PLC/PRF/5 hepatocellular carcinoma (HCC) cell line. This was done by studying cytotoxicity by MTT assay and chromosome condensation assay, early apoptosis by annexin-Pi staining, and late apoptosis by live-dead assay. The cellular uptake study was performed by incorporating coumarin-6 (C6) fluorophore in place of SRFT in Pull-SA conjugates. A biodistribution study was conducted in Swiss-albino mice to assess the biocompatibility and targeting properties of SRFT and Pull-SA-SRFT to the liver and other organs at 1, 6, 24, and 48 h. Results:The characterization studies of the copolymer confirmed the successful conjugation of Pull-SA. The self-assembled amphiphilic nanocarrier could proficiently entrap the hydrophobic drug SRFT to obtain an entrapment efficiency of 95.6% (Pull-SA-SRFT). Characterization of the synthesized nanoparticles exhibited highly desirable nanoparticle characteristics. In vitro, apoptotic studies urged that Pull-SA-SRFT nanoparticle was delivered more efficiently to HCC than SRFT. The cellular uptake study performed, gave propitious results in 4 hrs. The biodistribution study conducted in immunocompetent mice suggested that Pull-SA-SRFT was delivered more than SRFT to the liver when compared to other organs, and that the system was biocompatible. Conclusion: Pull-SA-SRFT is a promisingly safe, biodegradable, cell-specific nanocarrier and a potential candidate to target hydrophobic drugs to HCC.

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Immune checkpoint inhibitors in HCC: Cellular, molecular and systemic data

Cited by 47 publications

References 224 publications

Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing

Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing

Identification of HM13 as a prognostic indicator and a predictive biomarker for immunotherapy in hepatocellular carcinoma

Sorafenib-Entrapped, Self-Assembled Pullulan–Stearic Acid Biopolymer-Derived Drug Delivery System to PLC/PRF/5 Hepatocellular Carcinoma Model

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