A large-scale immunoinformatics analysis of the human papillomaviruses reveals a common E5 oncoprotein-pattern to evade the immune response

Abstract Background: Immune checkpoints target regulatory pathways in T cells which enhance antitumor immune responses and elicit durable clinical responses . As a novel immune checkpoint, CD96 is an attractive key target for cancer immunotherapy. However, there is no integrative investigation of CD96 in glioma. Our study explored the relationship between CD96 expression and clinical prognosis in glioma. Methods: A total of 1,024 RNA and clinical data were enrolled in this study, including 325 samples from the Chinese Glioma Genome Atlas (CGGA) database and 699 samples from The Cancer Genome Atlas (TCGA) dataset. R language was used to perform statistical analysis and draw figures. Results: CD96 had a consistently positive relationship with glioblastoma and highly enriched in IDH-wildtype and mesenchymal subtype glioma. GO enrichment and GSVA analyses suggested that CD96 was more involved in immune functions, especially related to T cell-mediated immune response in glioma. Subsequent immune infiltration analysis manifes ted that CD96 was positively correlated with infiltrating levels of CD4+ T and CD8+ T cells, macrophages , neutrophils, and DCs in GBM and LGG. Additionally, CD96 was tightly associated with other immune checkpoints including PD-1 , CTLA-4 , TIGIT , and TIM-3 . Univariate and multivariate Cox analysis demonstrated that CD96 acts as an independent indicator of poor prognosis in glioma. Conclusion: CD96 expression was increased in malignant phenotype and negatively associated with overall survival (OS) in glioma. CD96 also showed a positive correlation with other immune checkpoints, immune response, and inflammatory activity. Our findings indicate that CD96 is a promising clinical target for further immunotherapeutic in glioma patients.

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Manipulation of JAK/STAT Signalling by High-Risk HPVs: Potential Therapeutic Targets for HPV-Associated Malignancies

Viruses ◽

10.3390/v12090977 ◽

2020 ◽

Vol 12 (9) ◽

pp. 977 ◽

Cited By ~ 1

Author(s):

Ethan L. Morgan ◽

Andrew Macdonald

Keyword(s):

Immune Response ◽

Cell Proliferation ◽

Significant Proportion ◽

Human Papillomaviruses ◽

Janus Kinase ◽

Signalling Pathways ◽

Proliferative Potential ◽

Promote Cell Proliferation ◽

Wide Range ◽

Stat Pathway

Human papillomaviruses (HPVs) are small, DNA viruses that cause around 5% of all cancers in humans, including almost all cervical cancer cases and a significant proportion of anogenital and oral cancers. The HPV oncoproteins E5, E6 and E7 manipulate cellular signalling pathways to evade the immune response and promote virus persistence. The Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway has emerged as a key mediator in a wide range of important biological signalling pathways, including cell proliferation, cell survival and the immune response. While STAT1 and STAT2 primarily drive immune signalling initiated by interferons, STAT3 and STAT5 have widely been linked to the survival and proliferative potential of a number of cancers. As such, the inhibition of STAT3 and STAT5 may offer a therapeutic benefit in HPV-associated cancers. In this review, we will discuss how HPV manipulates JAK/STAT signalling to evade the immune system and promote cell proliferation, enabling viral persistence and driving cancer development. We also discuss approaches to inhibit the JAK/STAT pathway and how these could potentially be used in the treatment of HPV-associated disease.

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Large Scale RNAi Reveals the Requirement of Nuclear Envelope Breakdown for Nuclear Import of Human Papillomaviruses

PLoS Pathogens ◽

10.1371/journal.ppat.1004162 ◽

2014 ◽

Vol 10 (5) ◽

pp. e1004162 ◽

Cited By ~ 87

Author(s):

Inci Aydin ◽

Susanne Weber ◽

Berend Snijder ◽

Pilar Samperio Ventayol ◽

Andreas Kühbacher ◽

...

Keyword(s):

Nuclear Envelope ◽

Nuclear Import ◽

Large Scale ◽

Human Papillomaviruses ◽

Nuclear Envelope Breakdown

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Phylogeny affects host's weight, immune response and parasitism in damselflies and dragonflies

Royal Society Open Science ◽

10.1098/rsos.160421 ◽

2016 ◽

Vol 3 (11) ◽

pp. 160421 ◽

Cited By ~ 9

Author(s):

Jaakko J. Ilvonen ◽

Jukka Suhonen

Keyword(s):

Immune Response ◽

Body Mass ◽

Large Scale ◽

Phylogenetic Signal ◽

Strong Association ◽

Immune Defence ◽

Water Mite ◽

Host Parasite ◽

The Relationship ◽

Dragonfly Species

Host–parasite interactions are an intriguing part of ecology, and understanding how hosts are able to withstand parasitic attacks, e.g. by allocating resources to immune defence, is important. Damselflies and dragonflies show a variety of parasitism patterns, but large-scale comparative immune defence studies are rare, and it is difficult to say what the interplay is between their immune defence and parasitism. The aim of this study was to find whether there are differences in immune response between different damselfly and dragonfly species and whether these could explain their levels of gregarine and water mite parasitism. Using an artificial pathogen, a piece of nylon filament, we measured the encapsulation response of 22 different damselfly and dragonfly species and found that (i) there are significant encapsulation differences between species, (ii) body mass has a strong association with encapsulation and parasite prevalences, (iii) body mass shows a strong phylogenetic signal, whereas encapsulation response and gregarine and water mite prevalences show weak signals, and (iv) associations between the traits are affected by phylogeny. We do not know what the relationship is between these four traits, but it seems clear that phylogeny plays a role in determining parasitism levels of damselflies and dragonflies.

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Inverse Vaccination to Silence Immunity to Myelin in Multiple Sclerosis

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100022435 ◽

2010 ◽

Vol 37 (S2) ◽

pp. S49-S58 ◽

Cited By ~ 2

Author(s):

Lawrence Steinman

Keyword(s):

Multiple Sclerosis ◽

Immune Response ◽

Clinical Trials ◽

Immune Responses ◽

Large Scale ◽

Adaptive Immune Response ◽

Antibody Responses ◽

Myelin Proteins ◽

Adaptive Immune ◽

Key Drivers

ABSTRACT:The adaptive immune response in multiple sclerosis is complex. We have devised large scale arrays to measure the antibody response to myelin proteins and lipids. Despite the widespread immune responses to myelin, we have devised an inverse vaccine aimed at turning off key drivers of this diverse response. Clinical trials in patients with multiple sclerosis show that it is possible to constrain antibody responses to myelin on a large scale with this approach.

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Large-scale genomic study reveals robust activation of the immune system following advanced Inner Engineering meditation retreat.

10.1101/2021.05.18.444668 ◽

2021 ◽

Author(s):

Vijayendran Chandran ◽

Mei-Ling Bermudez ◽

Mert Koka ◽

Dhanashri Pawale ◽

Ramana Vishnubhotla ◽

...

Keyword(s):

Multiple Sclerosis ◽

Immune Response ◽

Large Scale ◽

Molecular Mechanisms ◽

Positive Impact ◽

Core Network ◽

Protein Protein Interaction ◽

Genomic Study ◽

Meditation Retreat ◽

Significant Expression

The positive impact of meditation on human wellbeing is well documented, yet its molecular mechanisms are incompletely understood. We applied a comprehensive systems biology approach starting with whole blood gene expression profiling combined with multi-level bioinformatic analyses to characterize the co-expression, transcriptional, and protein-protein interaction networks to identify meditation-specific core network after an advanced 8-day Inner Engineering retreat program. We found the response to oxidative stress, detoxification, and cell cycle regulation pathways were downregulated after meditation. Strikingly, 220 genes directly associated with immune response, including 68 genes related to interferon (IFN) signaling were upregulated, with no significant expression changes in the inflammatory genes. This robust meditation-specific immune response network is significantly dysregulated in multiple sclerosis and severe COVID-19 patients. The work provides a foundation for understanding the effect of meditation and potential implications to voluntarily and non-pharmacologically improve the immune response before immunotherapy for many conditions, including multiple sclerosis and COVID-19 vaccination.

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Large-scale genomic study reveals robust activation of the immune system following advanced Inner Engineering meditation retreat

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2110455118 ◽

2021 ◽

Vol 118 (51) ◽

pp. e2110455118

Author(s):

Vijayendran Chandran ◽

Mei-Ling Bermúdez ◽

Mert Koka ◽

Brindha Chandran ◽

Dhanashri Pawale ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Large Scale ◽

Molecular Mechanisms ◽

Positive Impact ◽

Well Being ◽

Core Network ◽

Protein Protein Interaction ◽

Genomic Study ◽

Meditation Retreat

The positive impact of meditation on human well-being is well documented, yet its molecular mechanisms are incompletely understood. We applied a comprehensive systems biology approach starting with whole-blood gene expression profiling combined with multilevel bioinformatic analyses to characterize the coexpression, transcriptional, and protein–protein interaction networks to identify a meditation-specific core network after an advanced 8-d Inner Engineering retreat program. We found the response to oxidative stress, detoxification, and cell cycle regulation pathways were down-regulated after meditation. Strikingly, 220 genes directly associated with immune response, including 68 genes related to interferon signaling, were up-regulated, with no significant expression changes in the inflammatory genes. This robust meditation-specific immune response network is significantly dysregulated in multiple sclerosis and severe COVID-19 patients. The work provides a foundation for understanding the effect of meditation and suggests that meditation as a behavioral intervention can voluntarily and nonpharmacologically improve the immune response for treating various conditions associated with excessive or persistent inflammation with a dampened immune system profile.

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A large-scale database of T-cell receptor beta (TCRβ) sequences and binding associations from natural and synthetic exposure to SARS-CoV-2.

10.21203/rs.3.rs-51964/v1 ◽

2020 ◽

Cited By ~ 2

Author(s):

Sean Nolan ◽

Marissa Vignali ◽

Mark Klinger ◽

Jennifer N. Dines ◽

Ian M. Kaplan ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

T Cell Receptor ◽

Large Scale ◽

Cell Receptor ◽

High Confidence ◽

T Cell Receptor Beta ◽

Current Content ◽

Receptor Beta ◽

Natural And Synthetic

Abstract We describe the establishment and current content of the ImmuneCODE™ database, which includes hundreds of millions of T-cell Receptor (TCR) sequences from over 1,400 subjects exposed to or infected with the SARS-CoV-2 virus, as well as over 135,000 high-confidence SARS-CoV-2-specific TCRs. This database is made freely available, and the data contained in it can be downloaded and analyzed online or offline to assist with the global efforts to understand the immune response to the SARS-CoV-2 virus and develop new interventions.

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