Intrahepatic landscape of regulatory T-cell subsets in chronically HCV-infected patients with cirrhosis and HCC

Wang, Xiaofan; Korangy, Firouzeh

doi:10.1002/hep.27271

Cited by 5 publications

(6 citation statements)

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“…In parallel, potential persistence of T regs activity may lead to immune evasion of cancerous cells and thus persistence of the carcinomatous conditions (13,14). Reports exist that the number of T regulatory cells may not be altered in HCC, either in the local tumor environment or in the peripheral circulating blood (15,16).…”

Section: Introductionmentioning

confidence: 99%

T_reg‐specific demethylated region activity in isolated regulatory t lymphocytes is a surrogate for disease severity in hepatocellular carcinoma

Liu

2015

IUBMB Life

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In certain unique conditions like viral infections of the liver like hepatitis B (HBV) and hepatitis C (HCV), activation of T regs may be associated with chronicity of the viral infections and subsequent predisposition to development of hepatocellular carcinoma (HCC) by the integrated viral genome. In parallel, potential persistence of T regs activity may lead to immune evasion of cancerous cells and thus persistence of the carcinomatous conditions. In this study, we hypothesized that although the relative proportions of T regs may remain unaltered in HCC, persistence of activity of T regs may lead to immune evasion in advanced stages of HCC. To examine the issue of activation of T reg in liver cancer pathogenesis, we obtained liver biopsy and peripheral blood samples from patients with advanced grades of HCC, isolated T regs , and examined the methylation status of "T reg -specific demethylated region" (TSDR), a key region whose methylation suppresses Treg activity and demethylation stimulates its genomic activity. This study provides evidence of demethylation of TSDR, increased gene expression examined by luciferase assays, and nuclear translocation of key transcription factors that function as gene enhancers in CD41CD251FoxP3 regulatory T cells in advanced grades of HCC. V C 2015 IUBMB Life, 67(5): [355][356][357][358][359][360] 2015

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Section: Introductionmentioning

confidence: 99%

T_reg‐specific demethylated region activity in isolated regulatory t lymphocytes is a surrogate for disease severity in hepatocellular carcinoma

Liu

2015

IUBMB Life

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“…36 DOCK2 has been identified as a potential marker for CD8 + T cell infiltration in HCC. 37 In addition, antigen presentation by MHC class II (HLA-DMB, HLA-DRA, HLA-DRB5) is activated in LR-HCC. The rest of the HCC-associated proteins, GRB2, SHC1, RAC2, SYK, PDIA3, LILRB1 and WASL that TILs respond to are highly related to liver disease and are likely to be tumour antigens of TILs.…”

Section: Protein-protein Interaction Network Of Tumour-infiltrating L...mentioning

confidence: 99%

Characterization of lymphocyte‐rich hepatocellular carcinoma and the prognostic role of tertiary lymphoid structures

Ahn,

Shin

et al. 2024

Liver International

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Background & AimsLymphocyte‐rich hepatocellular carcinoma (LR‐HCC) is largely unknown and a rare subtype of HCC with immune‐rich stroma. Tertiary lymphoid structures (TLS), frequently observed in LR‐HCC, are known to be prognostically significant in various malignancies; however, their significance in HCC remains unevaluated.MethodsClinicopathologic data of 191 cases of surgically resected conventional HCC (C‐HCC, n = 160) and LR‐HCC (n = 31) were retrieved. Immunohistochemistry, multiplex immunofluorescence staining, RNA sequencing and proteomic analysis were conducted. Differences between the subtypes were statistically evaluated.ResultsLR‐HCC was significantly correlated to larger tumour size, higher Edmondson–Steiner grade, presence of TLS and higher CD3‐, CD8‐ and FOXP3‐positive T cell, high PD‐1 and PD‐L1 expression (p < .001 for all) compared to C‐HCC. Patients with LR‐HCC exhibited significantly better overall survival (OS) (p = .044) and recurrence‐free survival (RFS) (p = .025) than C‐HCC. LR‐HCC demonstrated TLS signatures with significantly higher proteomic‐based immune scores in 14 of 17 types of tumour‐infiltrating immune cells. Furthermore, C‐HCC with secondary follicles, the most mature form of TLS, exhibited significantly better OS (p = .031) and RFS (p = .033) than those without. Across the global proteome, LR‐HCC was well‐differentiated from C‐HCC and a map of protein–protein interactions between tumour‐infiltrating lymphocytes and HCC in tumour microenvironment was completed.ConclusionLR‐HCC is clinicopathologically and molecularly distinct and shows better prognosis compared to C‐HCC. Also, the presence of secondary follicle can be an important prognostic marker for better prognosis in both LR‐HCC and C‐HCC.

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“…They identified that CD8 + T-cell exhaustion mediated by DOCK2 inactivation can be reversed by tolazamide. 125 As an RNA-binding protein that regulates neuronal RNA stability and translation, fragile X mental retardation protein (FMRP), is highly expressed in human cancers and may function in antitumor immunity. Mechanistically, immunosuppression of FMRP involves the repression of the chemoattractant CCL7 concomitant with the upregulation of three immunomodulators, IL-33, tumor-secreted protein S, and EVs.…”

Section: Genes Orchestrating Tumor Cells To Elicit Immune Conversionmentioning

confidence: 99%

“…Wang and colleagues revealed that the exhaustion of infiltrated CD8 + T cell in tumors is related to suppressed DOCK2 enzymatic activity in T cells in hepatocellular carcinoma (HCC), which is mediated by cholesterol sulfate synthesized by sulfotransferase 2B1 (SULT2B1) in tumor cells. They identified that CD8 + T‐cell exhaustion mediated by DOCK2 inactivation can be reversed by tolazamide 125 . As an RNA‐binding protein that regulates neuronal RNA stability and translation, fragile X mental retardation protein (FMRP), is highly expressed in human cancers and may function in antitumor immunity.…”

Section: Potential Targets Modulating Tumor Immune Responsementioning

confidence: 99%

Targets of tumor microenvironment for potential drug development

Zhang,

Wang,

Liu

et al. 2024

MedComm – Oncology

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The tumor microenvironment (TME) is the ecosystem surrounding a tumor, which usually consists of nontumoral cells or components, and molecules they produce and release. The frequent and continuous interplay between tumor cells and the TME strongly affects tumor development, disease progression, metastasis, and responses to therapeutic interventions. As a hub of potential therapeutic targets, the TME has gained appreciable momentum in cancer research. Here we systematically review the progress in targeting the TME as a strategy to develop novel antitumor drugs from the immunological, stromal and extracellular matrix components of the TME, shedding light on its complex synergies with tumor cells. This exploration highlights the transformative potential these elements hold in refining cancer treatment approaches. This thorough examination not only accentuates the TME's multifaceted nature but also positions it as a formidable avenue for propelling forward the paradigms of cancer therapy. This review aims to foster a deeper understanding of the TME's role in oncogenesis and its potential exploitation in advancing targeted, efficacious cancer treatments, marking a significant stride in the realm of cancer research.

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Intrahepatic landscape of regulatory T-cell subsets in chronically HCV-infected patients with cirrhosis and HCC

Cited by 5 publications

References 5 publications

T_reg‐specific demethylated region activity in isolated regulatory t lymphocytes is a surrogate for disease severity in hepatocellular carcinoma

T_reg‐specific demethylated region activity in isolated regulatory t lymphocytes is a surrogate for disease severity in hepatocellular carcinoma

Characterization of lymphocyte‐rich hepatocellular carcinoma and the prognostic role of tertiary lymphoid structures

Targets of tumor microenvironment for potential drug development

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Intrahepatic landscape of regulatory T-cell subsets in chronically HCV-infected patients with cirrhosis and HCC

Cited by 5 publications

References 5 publications

Treg‐specific demethylated region activity in isolated regulatory t lymphocytes is a surrogate for disease severity in hepatocellular carcinoma

Treg‐specific demethylated region activity in isolated regulatory t lymphocytes is a surrogate for disease severity in hepatocellular carcinoma

Characterization of lymphocyte‐rich hepatocellular carcinoma and the prognostic role of tertiary lymphoid structures

Targets of tumor microenvironment for potential drug development

Contact Info

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Resources

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T_reg‐specific demethylated region activity in isolated regulatory t lymphocytes is a surrogate for disease severity in hepatocellular carcinoma

T_reg‐specific demethylated region activity in isolated regulatory t lymphocytes is a surrogate for disease severity in hepatocellular carcinoma