HPV16 drives cancer immune escape via NLRX1-mediated degradation of STING

Luo, Xiaobo; Donnelly, Christopher R.; Gong, Wang; Heath, Blake R.; Hao, Yuning; Donnelly, Lorenza A.; Moghbeli, Toktam; Tan, Yee Sun; Lin, Xin; Bellile, Emily L.; Kansy, Benjamin; Carey, Thomas E.; Brenner, J. Chad; Cheng, Lei; Polverini, Peter J.; Morgan, Meredith A.; Wen, Haitao; Prince, Mark E.; Ferris, Robert L.; Xie, Yuying; Young, Simon; Wolf, Gregory T.; Chen, Qianming; Lei, Yu

doi:10.1172/jci129497

Cited by 124 publications

(138 citation statements)

References 60 publications

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“…Many pre-existing scientific researches have demonstrated that the occurrence and progression of tumors are strongly related to immune cells and chemokines in the human body (Han et al, 2019;Rosenthal et al, 2019), which can be verified through the mechanism of immune escape (Luo et al, 2019). In some diseases and tumor biological processes, the changes of these immune biomarkers are clear and even can be predicted in the immune microenvironment (Silva-Santos et al, 2019).…”

Section: Discussionmentioning

confidence: 98%

Prognostic Implications of Immune-Related Genes’ (IRGs) Signature Models in Cervical Cancer and Endometrial Cancer

Ding

Fan

et al. 2020

Front. Genet.

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Cervical cancer and endometrial cancer remain serious threats to women's health. Even though some patients can be treated with surgery plus chemoradiotherapy as a conventional option, the overall efficacy is deemed unsatisfactory. As such, the development for new treatment approaches is truly necessary. In recent years, immunotherapy has been widely used in clinical practice and it is an area of great interest that researchers are keeping attention on. However, a thorough immunerelated genes (IRGs) study for cervical cancer and endometrial cancer is still lacking. We therefore aim to make a comprehensive evaluation of IRGs through bioinformatics and large databases, and also investigate the relationship between the two types of cancer. We reviewed the transcriptome RNAs of IRGs and clinical data based on the TCGA database. Survival-associated IRGs in cervical/endometrial cancer were identified using univariable and multivariable Cox proportional-hazard regression analysis for developing an IRG signature model to evaluate the risk of patients. In the end, this model was validated based on the enrichment analyses through GO, KEGG, and GSEA pathways, Kaplan-Meier survival curve, ROC curves, and immune cell infiltration. Our results showed that out of 25/23 survival-associated IRGs for cervical/endometrial cancer, 13/12 warranted further examination by multivariate Cox proportional-hazard regression analysis and were selected to develop an IRGs signature model. As a result, enrichment analyses for high-risk groups indicated main enriched pathways were associated with tumor development and progression, and statistical differences were found between high-risk and low-risk groups as shown by Kaplan-Meier survival curve. This model could be used as an independent measure for risk assessment and was considered relevant to immune cell infiltration, but it had nothing to do with clinicopathological characteristics. In summary, based on comprehensive analysis, we obtained the IRGs signature model in cervical cancer (

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Section: Discussionmentioning

confidence: 98%

Prognostic Implications of Immune-Related Genes’ (IRGs) Signature Models in Cervical Cancer and Endometrial Cancer

Ding

Fan

et al. 2020

Front. Genet.

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“…E7 from the high-risk mucosal HPVs represses IRF1 activity, leading to decreased IFN-β gene expression [21,36,37]. Both high-risk mucosal HPV16 and HPV18 antagonize the adaptor protein within the dsDNA signaling pathway Stimulator of IFN genes (STING) to repress signaling through the cytosolic DNA receptor pathway, although they do this through different mechanisms [20,38]. Further, HPV18 E7 can epigenetically silence RIGI, the DNA sensor cyclic GMP-AMP synthase (cGAS), and STING preventing upregulation of IFN and IFN-stimulated genes activated by dsRNA and dsDNA [39].…”

Section: Discussionmentioning

confidence: 99%

Abrogation of Constitutive and Induced Type I and Type III Interferons and Interferon-Stimulated Genes in Keratinocytes by Canine Papillomavirus 2 E6 and E7

Quinlan

May

Weeks

et al. 2020

Viruses

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Cutaneous papillomaviruses can cause severe, persistent infections and skin cancer in immunodeficient patients, including people with X-linked severe combined immunodeficiency (XSCID). A similar phenotype is observed in a canine model of XSCID; these dogs acquire severe cutaneous papillomavirus infections that can progress to cancer in association with canine papillomavirus type 2 (CPV2). This canine model system provides a natural spontaneous animal model for investigation of papillomavirus infections in immunodeficient patients. Currently, it is unknown if CPV2 can subvert the innate immune system and interfere with its ability to express antiviral cytokines, which are critical in the host defense against viral pathogens. The aim of the current study was to determine if the oncogenes E6 and E7 from CPV2 interfere with expression of antiviral cytokines in keratinocytes, the target cells of papillomavirus infections. We determined that E6 but not E7 interferes with the constitutive expression of some antiviral cytokines, including interferon (IFN)-β and the IFN-stimulated gene IFIT1. Both E6 and E7 interfere with the transcriptional upregulation of the antiviral cytokines in response to stimulation with the dsDNA Poly(dA:dT). In contrast, while E6 also interferes with the transcriptional upregulation of antiviral cytokines in response to stimulation with the dsRNA Poly(I:C), E7 interferes with only a subset of these antiviral cytokines. Finally, we demonstrated that E7 but not E6 abrogates signaling through the type I IFN receptor. Taken together, CPV2 E6 and E7 both impact expression of antiviral cytokines in canine keratinocytes, albeit likely through different mechanisms.

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“…Many studies have reported the role of metabolism, RNA degradation and RNA transport in OSCC [34][35][36]. Human papillomavirus (HPV) is closely associated with OSCC [37]. HPV infection signi cantly increases the number of binding sites for RBPs and subsequently upregulates a group of oncogenic genes by absorbing RBPs [38].…”

Section: Discussionmentioning

confidence: 99%

A Novel Prognostic Model In Oral Squamous Carcinoma: The Functions And Prognostic Values Of Rna Binding Proteins

Yan

Liu

et al. 2020

Preprint

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Background: The biological roles and clinical significance of RNA-binding proteins (RBPs) in oral squamous cell carcinoma (OSCC) are not fully understood. We investigated the prognostic value of RBPs in OSCC by several bioinformatic strategies.Methods: OSCC data were obtained from a public online database, the Limma R package was used to identify differentially expressed RBPs, and functional enrichment analysis was performed to elucidate the biological functions of the above RBPs in OSCC. We performed protein-protein interaction (PPI) network and Cox regression analyses to extract prognosis-related hub RBPs. Next, we established and validated a prognostic model based on the hub RBPs by Cox regression and risk score analyses.Results: We found that the differentially expressed RBPs were closely related to the defence response to virus and multiple RNA processes. We obtained ten prognosis-related hub RBPs (ZC3H12D, OAS2, INTS10, ACO1, PCBP4, RNASE3, PTGES3L-AARSD1, RNASE13, DDX4, and PCF11) and effectively predicted the overall survival of OSCC patients. The area under the ROC curve (AUC) of the risk score model was 0.781, suggesting that our model had good prognostic performance. Finally, we built a nomogram integrating the ten RBPs. The internal validation cohort results showed a reliable predictive capability of the nomogram for OSCC.Conclusions: We established a novel ten-RBP-based model for OSCC that could enable precise therapeutic targets in the future.

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HPV16 drives cancer immune escape via NLRX1-mediated degradation of STING

Cited by 124 publications

References 60 publications

Prognostic Implications of Immune-Related Genes’ (IRGs) Signature Models in Cervical Cancer and Endometrial Cancer

Prognostic Implications of Immune-Related Genes’ (IRGs) Signature Models in Cervical Cancer and Endometrial Cancer

Abrogation of Constitutive and Induced Type I and Type III Interferons and Interferon-Stimulated Genes in Keratinocytes by Canine Papillomavirus 2 E6 and E7

A Novel Prognostic Model In Oral Squamous Carcinoma: The Functions And Prognostic Values Of Rna Binding Proteins

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