Immunobiology of hepatocarcinogenesis: Ways to go or almost there?

Patel, Pavan; Schutzer, Steven E.; Pyrsopoulos, Nikolaos

doi:10.4291/wjgp.v7.i3.242

Cited by 12 publications

(14 citation statements)

References 180 publications

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“…3 HCC development is a complex process involving multiple factors and pathways that lead to changes in gene expression, immune interactions, and changes in the tumor microenvironment that ultimately cause hepatocarcinogenesis. 4 Screening for HCC in high-risk populations has become the standard of care, requiring imaging with ultrasound, computerized tomography, or magnetic resonance imaging every 6-12 months. 5 Laboratory tests, including mainly those for alpha feto-protein, the lectin Lens culinaris agglutinin-bound fraction of alpha feto-protein-3, and des-gamma-carboxy prothrombin, are used in conjunction with imaging to establish the diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Management and Treatment of Hepatocellular Carcinoma with Immunotherapy: A Review of Current and Future Options

Ghavimi¹,

Apfel²,

Azimi³

et al. 2020

Journal of Clinical and Translational Hepatology

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With mortality rates of liver cancer doubling in the last 20 years, this disease is on the rise and has become the fifth most common cancer in men and the seventh most common cancer in women. Hepatocellular carcinoma (HCC) represents approximately 90% of all primary liver cancers and is a major global health concern. Patients with HCC can be managed curatively with surgical resection or with liver transplantation, if they are diagnosed at an early stage. Unfortunately, most patients with HCC present with advanced stages of the disease and have underlying liver dysfunction, which allows only 15% of patients to be eligible for curative treatment. Several different treatment modalities are available, including locoregional therapy radiofrequency ablation, microwave ablation, percutaneous ethanol injection, trans-arterial chemoembolization, transarterial radio-embolization, cryoablation, radiation therapy, stereotactic radiotherapy, systemic chemotherapy, molecularly targeted therapies, and immunotherapy. Immunotherapy has recently become a promising method for inhibiting HCC tumor progression, recurrence, and metastasis. The term "Immunotherapy" is a catch-all, encompassing a wide range of applications and targets, including HCC vaccines, adoptive cell therapy, immune checkpoint inhibitors, and use of oncolytic viruses to treat HCC. Immunotherapy in HCC is a relatively safe option for treating patients with advanced disease in the USA who are either unable to receive or failed sorafenib/lenvatinib therapy and thus may offer an additional survival benefit for these patients. The purpose of this review is to elaborate on some of the most recent advancements in immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Management and Treatment of Hepatocellular Carcinoma with Immunotherapy: A Review of Current and Future Options

Ghavimi¹,

Apfel²,

Azimi³

et al. 2020

Journal of Clinical and Translational Hepatology

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“…On the level of M1 macrophages, they exhibit a typical pro-inflammatory cytokine and chemokine profile: TNF- α, IL-1, IL-6, IL-12, IL-18, IL-23, MCP-1, CXCL9 and CXCL10. As for M2 macrophages, they are known for the secretion of IL-10, IL-12 low , CCL17, CCL22 and CCL24 [ 104 , 105 ]. M2 macrophages are active effectors in the context of HCC.…”

Section: Tackling the Crosstalk Between The Tumor And Its Microenvmentioning

confidence: 99%

“…Therefore, GRK2 siRNA was used to examine the molecular interactions of TNF-α in tumor growth, and the obtained results suggested that TNF-α could serve as a new potential therapeutic target in HCC [ 114 ]. TAMs also secrete a variety of growth factors such as TGF-β, VEGF, FGF, PDGF, angiogenic factor thymidine phosphorylase, angiogenesis-modulating enzyme cyclooxygenase-2, MMP-9 and MMP-12 [ 105 , 115 ]. On the level of immune response modulation, TAMs have been shown to suppress CD4 + CD25 − T cells, activate T-regs and contribute to the expansion of Th-17 cells, which, in turn, favor the expression of the immune-suppressing antigens PD-1, CTLA-4 and glucocorticoid-induced TNF receptor family-related (GTIR) [ 116 , 117 ].…”

Section: Tackling the Crosstalk Between The Tumor And Its Microenvmentioning

confidence: 99%

“…Natural killer (NK) cells are prominent in the liver and are the first responders against viral infections (HBV and HCV). NK cells are also in charge of maintaining proper immune function as they regulate the tuning of the immune response between the defensive and tolerance modes [ 105 , 133 ]. The inhibitory function of NK cells in HCC supports the tumor thriving.…”

Section: Tackling the Crosstalk Between The Tumor And Its Microenvmentioning

confidence: 99%

“…Interestingly, the RNAi-mediated suppression of HIF-1α expression in the liver inhibited metastatic tumor growth in the hepatoma cell line (SMMC-7721) and tumor-bearing mouse liver [ 135 , 136 ]. NK cells can be inhibited by HCC cells as HCC cells express major histocompatibility complex (MHC) class I polypeptide–related sequence A, a specific NK cell ligand that inhibits NK cell interaction [ 91 , 105 ]. Another mechanism of the depotentiation of NK cells by HCC cells is the impairment of IL-12 secretion by DCs by HCC cell-derived α-fetoprotein (AFP).…”

Section: Tackling the Crosstalk Between The Tumor And Its Microenvmentioning

confidence: 99%

See 2 more Smart Citations

Modulating the Crosstalk between the Tumor and Its Microenvironment Using RNA Interference: A Treatment Strategy for Hepatocellular Carcinoma

Mroweh

Decaens

Marche

et al. 2020

IJMS

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Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with one of the highest mortality rates among solid cancers. It develops almost exclusively in the background of chronic liver inflammation, which can be caused by viral hepatitis, chronic alcohol consumption or an unhealthy diet. Chronic inflammation deregulates the innate and adaptive immune responses that contribute to the proliferation, survival and migration of tumor cells. The continuous communication between the tumor and its microenvironment components serves as the overriding force of the tumor against the body’s defenses. The importance of this crosstalk between the tumor microenvironment and immune cells in the process of hepatocarcinogenesis has been shown, and therapeutic strategies modulating this communication have improved the outcomes of patients with liver cancer. To target this communication, an RNA interference (RNAi)-based approach can be used, an innovative and promising strategy that can disrupt the crosstalk at the transcriptomic level. Moreover, RNAi offers the advantage of specificity in comparison to the treatments currently used for HCC in clinics. In this review, we will provide the recent data pertaining to the modulation of a tumor and its microenvironment by using RNAi and its potential for therapeutic intervention in HCC.

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Core-shell nanomaterials engineered to reverse cancer multidrug resistance by immunotherapy and promote photo-responsive chemotherapy

Yan

Han

et al. 2022

Chemical Engineering Journal

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Immunobiology of hepatocarcinogenesis: Ways to go or almost there?

Cited by 12 publications

References 180 publications

Management and Treatment of Hepatocellular Carcinoma with Immunotherapy: A Review of Current and Future Options

Management and Treatment of Hepatocellular Carcinoma with Immunotherapy: A Review of Current and Future Options

Modulating the Crosstalk between the Tumor and Its Microenvironment Using RNA Interference: A Treatment Strategy for Hepatocellular Carcinoma

Core-shell nanomaterials engineered to reverse cancer multidrug resistance by immunotherapy and promote photo-responsive chemotherapy

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