Induction of cellular immunosuppression by the human papillomavirus type 16 E7 oncogenic protein

Buanec, Hélène Le; Lachgar, A; D'Anna, Rossella; Zagury, Jean‐François; Bizzini, B; Bernard, Jacky; Ittelé, D.; Hallez, Sophie; Giannouli, N.; Burny, Arsène; Zagury, Daniel

doi:10.1016/s0753-3322(00)88505-4

Cited by 17 publications

(5 citation statements)

References 20 publications

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“…disease progression (30). The minute amounts of E6 and E7 proteins in culture supernatant of SiHa cell were previously reported using the same dot ELISA (53,54). Although the exact mechanism of the presence of E6 and E7 protein in extracellular compartment was not known, whether actively exported or passively diffused, the circulating E6 and E7 protein might play a role in immunomodulation.…”

Section: Discussionmentioning

confidence: 59%

Both E6 and E7 Oncoproteins of Human Papillomavirus 16 Inhibit IL-18-Induced IFN-γ Production in Human Peripheral Blood Mononuclear and NK Cells

Lee

Cho

et al. 2001

The Journal of Immunology

108

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Cervical carcinoma is the predominant cancer among malignancies in women throughout the world, and human papillomavirus (HPV) 16 is the most common agent linked to human cervical carcinoma. The present study was performed to investigate the mechanisms of immune escape in HPV-induced cervical cancer cells. The presence of HPV oncoproteins E6 and E7 in the extracellular fluids of HPV-containing cervical cancer cell lines SiHa and CaSki was demonstrated by ELISA. The effect of HPV 16 oncoproteins E6 and E7 on the production of IFN-γ by IL-18 was assessed. E6 and E7 proteins reduced IL-18-induced IFN-γ production in both primary PBMCs and the NK0 cell line. FACS analysis revealed that the viral oncoproteins reduced the binding of IL-18 to its cellular surface receptors on NK0 cells, whereas there was no effect of oncoproteins on IL-1 binding to its surface IL-1 receptors on D10S, a subclone of the murine Th cell D10.G4.1. In vitro pull-down assays also revealed that the viral oncoproteins and IL-18 bound to IL-18R α-chain competitively. These results suggest that the extracellular HPV 16 E6 and E7 proteins may inhibit IL-18-induced IFN-γ production locally in HPV lesions through inhibition of IL-18 binding to its α-chain receptor. Down-modulation of IL-18-induced immune responses by HPV oncoproteins may contribute to viral pathogenesis or carcinogenesis.

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Section: Discussionmentioning

confidence: 59%

Both E6 and E7 Oncoproteins of Human Papillomavirus 16 Inhibit IL-18-Induced IFN-γ Production in Human Peripheral Blood Mononuclear and NK Cells

Lee

Cho

et al. 2001

The Journal of Immunology

108

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“…Multiple oncogenic viruses specifically inactivate RB, whereas others, such as hepatitis B and C, have been speculated to inactivate RB by way of indirect mechanisms such as sequestration or nuclear export . Interestingly, expression of a large subset of immune response genes are attenuated in cancers resulting from these viruses …”

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confidence: 99%

“…6,7 Interestingly, expression of a large subset of immune response genes are attenuated in cancers resulting from these viruses. 8 The liver is constantly exposed to pathogens and must deftly distinguish tolerable agents from pathogens. Hepatocytes are capable of binding Toll-like receptor (TLR) ligands 9,10 as well as presenting exogenous antigens.…”

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confidence: 99%

Retinoblastoma protein potentiates the innate immune response in hepatocytes: Significance for hepatocellular carcinoma

et al. 2014

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Cancers mediated by viral etiology must exhibit deregulated cellular proliferation and evade immune recognition. The role of the retinoblastoma tumor suppressor (RB) pathway, which is lost at relatively high frequency in HCC, has recently been expanded to include the regulation of innate immune responsiveness. In this study, we investigated the coordinate impact of RB-loss on cell cycle control and immune function in the liver. We found that RB depletion in hepatoma cells resulted in a compromised immunological response to multiple stimuli and reduced the potential of these cells to recruit myeloid cells. Viral-mediated liver-specific RB deletion in vivo led to the induction of genes associated with proliferation and cell cycle entry as well as the significant attenuation of genes associated with immune function, as evidenced by decreases in cytokine and chemokine expression, leukocyte recruitment and hepatic inflammation. To determine if these changes in gene expression were instructive in human disease, we compared our liver-specific RB-loss gene signature to existing profiles of HCC and found that this signature was associated with disease progression and confers a worse prognosis. Conclusion Our data confirm that RB participates in the regulation of innate immunity in liver parenchymal cells both in vitro and in vivo and to our knowledge describes the first gene signature associated with HCC that includes both immunoregulatory and proliferative genes and that can also be attributed to the alteration of a single gene in vitro.

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“…The possibility that E6 and E7 transcripts and/or proteins may be transferred to cells via microvesicles would not only provide a potential mechanistic basis for epithelial–stromal crosstalk, but would also represent a major paradigm shift in our understanding of HPV-associated disease. In this regard, reports from one lab that E6 and E7 can be detected in the extracellular space and purified protein can be internalized by endothelial cells is particularly intriguing [ 139 , 140 , 141 ]. Furthermore, our own recent unpublished studies indicate that in vivo expression of the HPV oncogenes in the cervical epithelium has a profound, cell non-autonomous effect on global gene expression in nearby stromal cells [ 89 ].…”

Section: Potential Mechanisms Of Bidirectional Crosstalkmentioning

confidence: 99%

Human Papillomavirus and the Stroma: Bidirectional Crosstalk during the Virus Life Cycle and Carcinogenesis

Spurgeon

Lambert

2017

Viruses

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Human papillomaviruses (HPVs) are double-stranded DNA (dsDNA) tumor viruses that are causally associated with human cancers of the anogenital tract, skin, and oral cavity. Despite the availability of prophylactic vaccines, HPVs remain a major global health issue due to inadequate vaccine availability and vaccination coverage. The HPV life cycle is established and completed in the terminally differentiating stratified epithelia, and decades of research using in vitro organotypic raft cultures and in vivo genetically engineered mouse models have contributed to our understanding of the interactions between HPVs and the epithelium. More recently, important and emerging roles for the underlying stroma, or microenvironment, during the HPV life cycle and HPV-induced disease have become clear. This review discusses the current understanding of the bidirectional communication and relationship between HPV-infected epithelia and the surrounding microenvironment. As is the case with other human cancers, evidence suggests that the stroma functions as a significant partner in tumorigenesis and helps facilitate the oncogenic potential of HPVs in the stratified epithelium.

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Induction of cellular immunosuppression by the human papillomavirus type 16 E7 oncogenic protein

Cited by 17 publications

References 20 publications

Both E6 and E7 Oncoproteins of Human Papillomavirus 16 Inhibit IL-18-Induced IFN-γ Production in Human Peripheral Blood Mononuclear and NK Cells

Both E6 and E7 Oncoproteins of Human Papillomavirus 16 Inhibit IL-18-Induced IFN-γ Production in Human Peripheral Blood Mononuclear and NK Cells

Retinoblastoma protein potentiates the innate immune response in hepatocytes: Significance for hepatocellular carcinoma

Human Papillomavirus and the Stroma: Bidirectional Crosstalk during the Virus Life Cycle and Carcinogenesis

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