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Article: Human Papillomavirus-Associated Tumor Extracellular Vesicles in HPV

Gameiro, Steven F / Flondra, Kaitlyn M

2023 Volume 12, Issue 17

Abstract: Most infections with human papillomaviruses (HPVs) are self-resolving and asymptomatic. However, some infections can lead to the development of cancer at different mucosal sites, such as the cervix and the head and neck. Head and neck cancers (HNCs) are ... ...

Abstract	Most infections with human papillomaviruses (HPVs) are self-resolving and asymptomatic. However, some infections can lead to the development of cancer at different mucosal sites, such as the cervix and the head and neck. Head and neck cancers (HNCs) are dichotomized into HPV-positive (HPV
Language	English
Publishing date	2023-08-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12175668
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Special Issue "Human Papillomavirus Clinical Research: From Infection to Cancer".

Gameiro, Steven F / Mymryk, Joe S

Journal of clinical medicine

2022 Volume 11, Issue 14

Abstract: Papillomaviruses (PVs) are ubiquitous intracellular pathogens that have co-evolved with many different species [ ... ]. ...

Abstract	Papillomaviruses (PVs) are ubiquitous intracellular pathogens that have co-evolved with many different species [...].
Language	English
Publishing date	2022-07-21
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11144225
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Article ; Online: The tumor immune microenvironments of HPV

Gameiro, Steven F / Evans, Andris M / Mymryk, Joe S

WIREs mechanisms of disease

2021 Volume 14, Issue 2, Page(s) e1539

Abstract: Human papillomaviruses (HPVs) are the etiological agent of a significant, and increasing, fraction of head and neck squamous cell carcinomas (HNSCC)-a heterogenous group of malignancies in the head and neck region. HPV infection accounts for ... ...

Abstract	Human papillomaviruses (HPVs) are the etiological agent of a significant, and increasing, fraction of head and neck squamous cell carcinomas (HNSCC)-a heterogenous group of malignancies in the head and neck region. HPV infection accounts for approximately 25% of all cases, with the remainder typically caused by smoking and excessive alcohol consumption. These distinct etiologies lead to profound clinical and immunological differences between HPV-positive (HPV
MeSH term(s)	Alphapapillomavirus ; Head and Neck Neoplasms ; Humans ; Papillomaviridae ; Papillomavirus Infections/complications ; Squamous Cell Carcinoma of Head and Neck ; Tumor Microenvironment
Language	English
Publishing date	2021-10-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	2692-9368
ISSN (online)	2692-9368
DOI	10.1002/wsbm.1539
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Article: HPV-Positive and -Negative Cervical Cancers Are Immunologically Distinct.

Evans, Andris M / Salnikov, Mikhail / Gameiro, Steven F / Maleki Vareki, Saman / Mymryk, Joe S

Journal of clinical medicine

2022 Volume 11, Issue 16

Abstract: Although infection with human papillomavirus (HPV) is associated with nearly all cervical cancers (CC), a small proportion are HPV-negative. Recently, it has become clear that HPV-negative CC represent a distinct disease phenotype compared to HPV- ... ...

Abstract	Although infection with human papillomavirus (HPV) is associated with nearly all cervical cancers (CC), a small proportion are HPV-negative. Recently, it has become clear that HPV-negative CC represent a distinct disease phenotype compared to HPV-positive disease and exhibit increased mortality. In addition, variations between different HPV types associated with CC have been linked to altered molecular pathology and prognosis. We compared the immune microenvironments of CC caused by HPV α9 species (HPV16-like), HPV α7 species (HPV18-like) and HPV-negative disease. HPV-negative CC appeared distinct from other subtypes, with greatly reduced levels of lymphocyte infiltration compared to either HPV α9 or α7 CC. Besides reduced levels of markers indicative of B, T, and NK lymphocytes, the expression of T-cell effector molecules, activation/exhaustion markers, and T-cell receptor diversity were also significantly lower in HPV-negative CC. Interestingly, HPV-negative CC expressed much higher levels of potential neoantigens than HPV-positive CC. These results identify profound differences between the immune landscape of HPV-positive and HPV-negative CC as well as modest differences between HPV α9 and α7 CC. These differences may contribute to altered patient outcomes between HPV-negative and HPV-positive CC and potentially between CC associated with different HPV types.
Language	English
Publishing date	2022-08-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11164825
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Article ; Online: HPV16 Intratypic Variants in Head and Neck Cancers: A North American Perspective.

Gameiro, Steven F / Salnikov, Mikhail Y / Zeng, Peter Y F / Barrett, John W / Nichols, Anthony C / Mymryk, Joe S

Viruses

2023 Volume 15, Issue 12

Abstract: Human papillomavirus (HPV) is the major causative agent for cervical and many head and neck cancers (HNCs). HPVs randomly acquire single nucleotide polymorphisms (SNPs) that may become established via positive selection. Within an HPV type, viral ... ...

Abstract	Human papillomavirus (HPV) is the major causative agent for cervical and many head and neck cancers (HNCs). HPVs randomly acquire single nucleotide polymorphisms (SNPs) that may become established via positive selection. Within an HPV type, viral isolates differing by <2% in the L1 region are termed "variants" and classified based on combinations of SNPs. Studies in cervical cancer demonstrate clear differences between HPV16 intratypic variants in terms of persistence of infection, tumor histology, cancer risk, and death. Much less is known about the frequency of HPV16 variants in HNC, and their effects on clinical outcomes. We combined HPV16 positive (HPV16
MeSH term(s)	Female ; Humans ; Human papillomavirus 16/genetics ; Papillomavirus Infections ; Uterine Cervical Neoplasms ; Polymorphism, Single Nucleotide ; Head and Neck Neoplasms/genetics ; North America ; Ontario ; Oncogene Proteins, Viral/genetics
Chemical Substances	Oncogene Proteins, Viral
Language	English
Publishing date	2023-12-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15122411
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Article ; Online: The HPV Induced Cancer Resource (THInCR): a Suite of Tools for Investigating HPV-Dependent Human Carcinogenesis.

Salnikov, Mikhail / Gameiro, Steven F / Zeng, Peter Y F / Barrett, John W / Nichols, Anthony C / Mymryk, Joe S

mSphere

2022 Volume 7, Issue 4, Page(s) e0031722

Abstract: Human papillomaviruses (HPVs) are highly infectious and cause the most common sexually transmitted viral infections. They induce hyperproliferation of squamous epithelial tissue, often forming warts. Virally encoded proteins reprogram gene expression and ...

Abstract	Human papillomaviruses (HPVs) are highly infectious and cause the most common sexually transmitted viral infections. They induce hyperproliferation of squamous epithelial tissue, often forming warts. Virally encoded proteins reprogram gene expression and cell growth to create an optimal environment for viral replication. In addition to their normal roles in infection, functional alterations induced by viral proteins establish conditions that frequently contribute to human carcinogenesis. In fact, ~5% of human cancers are caused by HPVs, with virtually all cervical squamous cell carcinomas (CESC) and an increasing number of head and neck squamous cell carcinomas (HNSC) attributed to HPV infection. The Cancer Genome Atlas (TCGA) molecularly characterized thousands of primary human cancer samples in many cancer types, including CESC and HNSC, and created a comprehensive atlas of genomic, epigenomic, and transcriptomic data. This publicly available genome-wide information provides an unprecedented opportunity to expand the knowledge of the role that HPV plays in human carcinogenesis. While many tools exist to mine these data, few, if any, focus on the comparison of HPV-positive cancers with their HPV-negative counterparts or adjacent normal control tissue. We have constructed a suite of web-based tools, The HPV Induced Cancer Resource (THInCR), to utilize TCGA data for research related to HPV-induced CESC and HNSC. These tools allow investigators to gain greater biological and medical insights by exploring the impacts of HPV on cellular gene expression (mRNA and microRNA), altered gene methylation, and associations with patient survival and immune landscape features. These tools are accessible at https://thincr.ca/.
MeSH term(s)	Carcinogenesis/genetics ; Head and Neck Neoplasms/genetics ; Humans ; MicroRNAs/genetics ; Papillomaviridae/genetics ; Papillomavirus Infections/complications ; Papillomavirus Infections/pathology ; RNA, Messenger ; Squamous Cell Carcinoma of Head and Neck
Chemical Substances	MicroRNAs ; RNA, Messenger
Language	English
Publishing date	2022-08-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-5042
ISSN (online)	2379-5042
DOI	10.1128/msphere.00317-22
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Article ; Online: High Levels of Class I Major Histocompatibility Complex mRNA Are Present in Epstein-Barr Virus-Associated Gastric Adenocarcinomas.

Ghasemi, Farhad / Gameiro, Steven F / Tessier, Tanner M / Maciver, Allison H / Mymryk, Joe S

Cells

2020 Volume 9, Issue 2

Abstract: Epstein-Barr virus (EBV) is responsible for approximately 9% of stomach adenocarcinomas. EBV-encoded microRNAs have been reported as reducing the function of the class I major histocompatibility complex (MHC-I) antigen presentation apparatus, which could ...

Abstract	Epstein-Barr virus (EBV) is responsible for approximately 9% of stomach adenocarcinomas. EBV-encoded microRNAs have been reported as reducing the function of the class I major histocompatibility complex (MHC-I) antigen presentation apparatus, which could allow infected cells to evade adaptive immune responses. Using data from nearly 400 human gastric carcinomas (GCs), we assessed the impact of EBV on MHC-I heavy and light chain mRNA levels, as well as multiple other components essential for antigen processing and presentation. Unexpectedly, mRNA levels of these genes were as high, or higher, in EBV-associated gastric carcinomas (EBVaGCs) compared to normal control tissues or other GC subtypes. This coordinated upregulation could have been a consequence of the higher intratumoral levels of interferon γ in EBVaGCs, which correlated with signatures of increased infiltration by T and natural killer (NK) cells. These results indicate that EBV-encoded products do not effectively reduce mRNA levels of the MHC-I antigen presentation apparatus in human GCs.
MeSH term(s)	Adenocarcinoma/complications ; Adenocarcinoma/immunology ; Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/immunology ; Epstein-Barr Virus Infections/virology ; Female ; Genes, MHC Class I ; Herpesvirus 4, Human/immunology ; Histocompatibility Antigens Class I/genetics ; Humans ; Interferon-gamma/metabolism ; Lymphocytes/immunology ; Male ; Middle Aged ; RNA, Messenger/genetics ; Stomach Neoplasms/complications ; Stomach Neoplasms/immunology ; Tumor Escape/genetics
Chemical Substances	Histocompatibility Antigens Class I ; IFNG protein, human ; RNA, Messenger ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2020-02-21
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9020499
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Article: High Level Expression of MHC-II in HPV+ Head and Neck Cancers Suggests that Tumor Epithelial Cells Serve an Important Role as Accessory Antigen Presenting Cells.

Gameiro, Steven F / Ghasemi, Farhad / Barrett, John W / Nichols, Anthony C / Mymryk, Joe S

Cancers

2019 Volume 11, Issue 8

Abstract: High-risk human papillomaviruses (HPVs) are responsible for a subset of head and neck squamous cell carcinomas (HNSCC). Expression of class II major histocompatibility complex (MHC-II) is associated with antigen presenting cells (APCs). During ... ...

Abstract	High-risk human papillomaviruses (HPVs) are responsible for a subset of head and neck squamous cell carcinomas (HNSCC). Expression of class II major histocompatibility complex (MHC-II) is associated with antigen presenting cells (APCs). During inflammation, epithelial cells can be induced to express MHC-II and function as accessory APCs. Utilizing RNA-seq data from over 500 HNSCC patients from The Cancer Genome Atlas, we determined the impact of HPV-status on the expression of MHC-II genes and related genes involved in their regulation, antigen presentation, and T-cell co-stimulation. Expression of virtually all MHC-II genes was significantly upregulated in HPV+ carcinomas compared to HPV- or normal control tissue. Similarly, genes that encode products involved in antigen presentation were also significantly upregulated in the HPV+ cohort. In addition, the expression of
Language	English
Publishing date	2019-08-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers11081129
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Article ; Online: High MHC-II expression in Epstein-Barr virus-associated gastric cancers suggests that tumor cells serve an important role in antigen presentation.

Ghasemi, Farhad / Tessier, Tanner M / Gameiro, Steven F / Maciver, Allison H / Cecchini, Matthew J / Mymryk, Joe S

Scientific reports

2020 Volume 10, Issue 1, Page(s) 14786

Abstract: EBV-associated gastric adenocarcinomas (EBVaGCs) often exhibit better clinical outcomes than EBV negative gastric cancers (GCs), which could be related to their consistent expression of foreign viral antigens. Antigen-presenting cells (APCs) present ... ...

Abstract	EBV-associated gastric adenocarcinomas (EBVaGCs) often exhibit better clinical outcomes than EBV negative gastric cancers (GCs), which could be related to their consistent expression of foreign viral antigens. Antigen-presenting cells (APCs) present peptide antigens in the context of the class-II major histocompatibility complex (MHC-II). During inflammatory conditions, epithelial cells express MHC-II and function as accessory APCs. Utilizing RNA-seq data from nearly 400 GC patients, we determined the impact of EBV-status on expression of MHC-II components, genes involved in their regulation, and T-cell co-stimulation. Virtually all MHC-II genes were significantly upregulated in EBVaGCs compared to normal tissues, or other GC subtypes. Genes involved in antigen presentation were also significantly upregulated in EBVaGCs, as were the key MHC-II transcriptional regulators CIITA and RFX5. This was unexpected as the EBV encoded BZLF1 protein can repress CIITA transcription and is expressed in many EBVaGCs. Furthermore, MHC-II upregulation was strongly correlated with elevated intratumoral levels of interferon-gamma. In addition, expression of co-stimulatory molecules involved in T-cell activation and survival was also significantly increased in EBVaGCs. Thus, gastric adenocarcinoma cells may functionally contribute to the highly immunogenic tumor microenvironment observed in EBVaGCs via a previously unappreciated role in interferon-induced antigen presentation.
MeSH term(s)	Antigen Presentation/immunology ; Antigen-Presenting Cells/immunology ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/virology ; Herpesvirus 4, Human/isolation & purification ; Histocompatibility Antigens Class II/classification ; Histocompatibility Antigens Class II/genetics ; Histocompatibility Antigens Class II/metabolism ; Humans ; Stomach Neoplasms/immunology ; Stomach Neoplasms/pathology ; Stomach Neoplasms/virology ; Trans-Activators ; Tumor Microenvironment/immunology
Chemical Substances	Histocompatibility Antigens Class II ; Trans-Activators
Language	English
Publishing date	2020-09-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-71775-4
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Article ; Online: Hacking the Cell: Network Intrusion and Exploitation by Adenovirus E1A.

King, Cason R / Zhang, Ali / Tessier, Tanner M / Gameiro, Steven F / Mymryk, Joe S

mBio

2018 Volume 9, Issue 3

Abstract: As obligate intracellular parasites, viruses are dependent on their infected hosts for survival. Consequently, viruses are under enormous selective pressure to utilize available cellular components and processes to their own advantage. As most, if not ... ...

Abstract	As obligate intracellular parasites, viruses are dependent on their infected hosts for survival. Consequently, viruses are under enormous selective pressure to utilize available cellular components and processes to their own advantage. As most, if not all, cellular activities are regulated at some level via protein interactions, host protein interaction networks are particularly vulnerable to viral exploitation. Indeed, viral proteins frequently target highly connected "hub" proteins to "hack" the cellular network, defining the molecular basis for viral control over the host. This widespread and successful strategy of network intrusion and exploitation has evolved convergently among numerous genetically distinct viruses as a result of the endless evolutionary arms race between pathogens and hosts. Here we examine the means by which a particularly well-connected viral hub protein, human adenovirus E1A, compromises and exploits the vulnerabilities of eukaryotic protein interaction networks. Importantly, these interactions identify critical regulatory hubs in the human proteome and help define the molecular basis of their function.
MeSH term(s)	Adenoviridae/genetics ; Adenoviridae/metabolism ; Adenoviridae Infections/genetics ; Adenoviridae Infections/metabolism ; Adenoviridae Infections/virology ; Adenovirus E1A Proteins/genetics ; Adenovirus E1A Proteins/metabolism ; Animals ; Host-Pathogen Interactions ; Humans
Chemical Substances	Adenovirus E1A Proteins
Language	English
Publishing date	2018-05-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.00390-18
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