Adverse effects of PD-1 targeted immunotherapy in NAFLD-triggered HCC

Pfister, D.; Núñez, Natalia Fernández; Sinha, Anindita; Weiner, Assaf; Deczkowska, Aleksandra; Pinter, Matthias; Govaere, Olivier; Müller, Felicitas; Anstee, Quentin M.; Entgleitner, T; Rad, Roland; Pinyol, Roser; Torrecilla, Sara; Dudek, Michael; Knolle, Percy; Weber, Amy; Lengenhagger, D; Llovet, Josep M.; Amit, Ido; Meissner, Felix; Heikenwälder, M

doi:10.1055/a-1143-8420

Cited by 7 publications

(14 citation statements)

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“…Elucidating the molecular mechanisms of hepatocellular carcinoma remains an urgent clinical challenge. Currently, the therapeutic efficacy of available drugs for advanced liver cancer is limited (Faivre et al, 2020;Pfister et al, 2020). In recent years, lncRNA has aroused extensive research interest in various countries in the world.…”

Section: Discussionmentioning

confidence: 99%

lncRNA SNHG9 Promotes Cell Proliferation, Migration, and Invasion in Human Hepatocellular Carcinoma Cells by Increasing GSTP1 Methylation, as Revealed by CRISPR-dCas9

2021

Front. Mol. Biosci.

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Hepatocellular carcinoma (HCC) is among the major causes of cancer-related mortalities globally. Long non-coding RNAs (LncRNAs), as epigenetic molecules, contribute to malignant tumor incidences and development, including HCC. Although LncRNA SNHG9 is considered an oncogene in many cancers, the biological function and molecular mechanism of SNHG9 in HCC are still unclear. We investigated the effects of lncRNA SNHG9 on the methylation of glutathione S-transferase P1 (GSTP1) and the progression of HCC. Histological data analysis, CRISPR-dCas9, and cytological function experiment were used to study the expression level and biological function of SNHG9 in HCC. There was an upregulated expression of SNHG9 in HCC, which was associated with shorter disease-free survival. Knockdown of SNHG9 can inhibit cell proliferation, block cell cycle progression, and inhibit cell migration and invasion by upregulating GSTP1. LncRNA SNHG9 recruits methylated enzymes (DNMT1, DNMT3A, and DNMT3B) to increase GSTP1 promoter methylation, a common event in the development of HCC. Inhibition of lncRNA SNHG9 demethylates GSTP1, which prevents HCC progression, presents a promising therapeutic approach for HCC patients.

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Section: Discussionmentioning

confidence: 99%

lncRNA SNHG9 Promotes Cell Proliferation, Migration, and Invasion in Human Hepatocellular Carcinoma Cells by Increasing GSTP1 Methylation, as Revealed by CRISPR-dCas9

2021

Front. Mol. Biosci.

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“…105 140 MASH has been found to limit the efficiency of immunotherapy. 23 Compared with viral HCC, a reduction of GZMB + CD4 + /CD8 + T cells was observed in MASH-HCC by using spatial proteome analysis, whereas interactions of PD-1 + CD8 + T cells and PD-L1 + ICOS + MDSCs or TAMs were enriched, demonstrating an immunosuppressive microenvironment in MASH-HCC which may impede treatment response. 141 Therefore, understanding the etiology-related TIME in liver cancer may facilitate the development of effective treatment strategies with immunotherapy.…”

Section: Challenges and Opportunitiesmentioning

confidence: 91%

“…The heterogeneity of liver TIME among patients mainly reflects specific enrichment of certain immune cell states or related cellular communications, while the heterogeneity within a patient indicates the diverse functional states of immune cells and their spatial relationships with the tumor. 22 23 24 25 26 In this review, we highlight the heterogeneity of the major immune cells in the liver TIME and provide an update on how the emerging single cell and spatial technologies unveil the heterogeneity and plasticity of each cell type. We also delve into the emergent properties of the cellular networks in regulating immune responses in the context of liver cancer.…”

Section: Lay Summarymentioning

confidence: 99%

Heterogeneity in Liver Cancer Immune Microenvironment: Emerging Single-Cell and Spatial Perspectives

Li,

Liu,

Lee

et al. 2024

Semin Liver Dis

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Primary liver cancer is a solid malignancy with a high mortality rate. The success of immunotherapy has shown great promise in improving patient care and highlights a crucial need to understand the complexity of the liver tumor immune microenvironment (TIME). Recent advances in single-cell and spatial omics technologies, coupled with the development of systems biology approaches, are rapidly transforming the landscape of tumor immunology. Here we review the cellular landscape of liver TIME from single-cell and spatial perspectives. We also discuss the cellular interaction networks within the tumor cell community in regulating immune responses. We further highlight the challenges and opportunities with implications for biomarker discovery, patient stratification, and combination immunotherapies.

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“…Depletion of CD8 + T cells limits HCC development according to many reports, but this is not always the case. 81 82 This may be due to the conflicting roles of CD8 + T cells in the MASH liver, such as the abovementioned proinflammatory and profibrogenic roles that promote hepatocarcinogenesis and the immune surveillance roles that prevent hepatocarcinogenesis. Recent reports have shown that the number of PD-1 + CD8 + T cells is increased in the liver of MASH-HCC patients, and anti-PD-1 therapy induces hepatic damage rather than exert antitumor effects.…”

Section: Inflammation and Immune Dysregulation In Metabolic-associate...mentioning

confidence: 99%

“…38 Taken together, these findings suggest that a steatotic environment, regardless of whether it is intrahepatic or intratumoral, may cause T-cell exhaustion in the liver, resulting in T-cell activation upon ICI therapy. 38 81…”

Section: Inflammation and Immune Dysregulation In Metabolic-associate...mentioning

confidence: 99%

Molecular Genealogy of Metabolic-associated Hepatocellular Carcinoma

Kodama,

Takehara

2024

Semin Liver Dis

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This review examines the latest epidemiological and molecular pathogenic findings of metabolic-associated hepatocellular carcinoma (HCC). Its increasing prevalence is a significant concern and reflects the growing burden of obesity and metabolic diseases, including metabolic dysfunction-associated steatotic liver disease, formerly known as nonalcoholic fatty liver disease, and type 2 diabetes. Metabolic-associated HCC has unique molecular abnormality and distinctive gene expression patterns implicating aberrations in bile acid, fatty acid metabolism, oxidative stress, and proinflammatory pathways. Furthermore, a notable frequency of single nucleotide polymorphisms in genes such as patatin-like phospholipase domain-containing 3, transmembrane 6 superfamily member 2, glucokinase regulator, and membrane-bound O-acyltransferase domain-containing 7 has been observed. The tumor immune microenvironment of metabolic-associated HCC is characterized by unique phenotypes of macrophages, neutrophils, and T lymphocytes. Additionally, the pathogenesis of metabolic-associated HCC is influenced by abnormal lipid metabolism, insulin resistance, and dysbiosis. In conclusion, deciphering the intricate interactions among metabolic processes, genetic predispositions, inflammatory responses, immune regulation, and microbial ecology is imperative for the development of novel therapeutic and preventative measures against metabolic-associated HCC.

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Adverse effects of PD-1 targeted immunotherapy in NAFLD-triggered HCC

Cited by 7 publications

References 0 publications

lncRNA SNHG9 Promotes Cell Proliferation, Migration, and Invasion in Human Hepatocellular Carcinoma Cells by Increasing GSTP1 Methylation, as Revealed by CRISPR-dCas9

lncRNA SNHG9 Promotes Cell Proliferation, Migration, and Invasion in Human Hepatocellular Carcinoma Cells by Increasing GSTP1 Methylation, as Revealed by CRISPR-dCas9

Heterogeneity in Liver Cancer Immune Microenvironment: Emerging Single-Cell and Spatial Perspectives

Molecular Genealogy of Metabolic-associated Hepatocellular Carcinoma

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