HPV-16 E5 down-regulates expression of surface HLA class I and reduces recognition by CD8 T cells

Campo, M. Saveria; Graham, Sheila V.; Cortese, Marc S.; Ashrafi, G. Hossein; Araibi, E. H.; Dornan, Edward S.; Miners, Kelly L.; Nunes, Claudia Trindade; Man, Stephen

doi:10.1016/j.virol.2010.07.044

Cited by 137 publications

(122 citation statements)

References 26 publications

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“…Similarly, about 25% of HNSCC tumors or more, dependent on their anatomic site, are associated with high-risk human papillomaviruses (HPV), in particular the type 16 (41). The papillomavirus oncoprotein E5 is implicated in MHC class I downregulation (42,43), and was shown to affect MHC class II maturation in IFNg-treated keratinocytes (44). Consistent with these reports, the VX2 carcinoma was found to express E5 mRNA at high levels (data not shown).…”

Section: Discussionsupporting

confidence: 53%

Intraperitoneal Oxidative Stress in Rabbits with Papillomavirus-Associated Head and Neck Cancer Induces Tumoricidal Immune Response That Is Adoptively Transferable

Rossmann

Mandic

Heinis

et al. 2014

Clinical Cancer Research

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Purpose: How tumors evade or suppress immune surveillance is a key question in cancer research, and overcoming immune escape is a major goal for lengthening remission after cancer treatment. Here, we used the papillomavirus-associated rabbit auricular VX2 carcinoma, a model for studying human head and neck cancer, to reveal the mechanisms underlying the antitumorigenic effects of intraperitoneal oxidative stressExperimental Design: Solid auricular VX2 tumors were induced in immune-competent adult New Zealand White Rabbits. Animals were O 3 /O 2 -PP-or sham-treated, after which they underwent tumor ablation upon reaching no-go criteria. CD3 þ tumor-infiltrating lymphocytes (TIL) were evaluated by immunohistochemistry, and expression levels of 84 immune response genes were measured by quantitative real-time PCR. Adoptive transfer of peripheral blood leukocytes (PBL)-derived from animals with tumor regression-into control animals with progressing tumors was implemented to assess acquired tumor resistance functionally. Results: Auricular VX2 tumors regressing after O 3 /O 2 -PP treatment exhibited increased levels of CD3 þ TILs; they also exhibited enhanced expression of genes that encode receptors involved in pattern recognition, molecules that are required for antigen presentation and T cell activation, and inflammatory mediators. Adoptive cell transfer of PBLs from donor rabbits with regressing tumors to recipient rabbits with newly implanted VX2 carcinoma resulted in acquired tumor resistance of the host and tumor regression. Conclusion: Intraperitoneal oxidative stress effectively converts the immune response against the papillomavirus-associated rabbit VX2 carcinoma from tumor permissive to tumoricidal and leads to a sustainable, adoptively transferable oncolytic immune response. Clin Cancer Res; 20(16); 4289-301. Ó2014 AACR.

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Section: Discussionsupporting

confidence: 53%

Intraperitoneal Oxidative Stress in Rabbits with Papillomavirus-Associated Head and Neck Cancer Induces Tumoricidal Immune Response That Is Adoptively Transferable

Rossmann

Mandic

Heinis

et al. 2014

Clinical Cancer Research

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“…43 The E5 expression was accompanied by a decreased expression of HLA-A2 and had a functional impact on recognition of E5 expressing cells by HPV specific CD81 T cells. 44 NK cells are usually rare in healthy skin. [45][46][47] This limits access to HPV-infected cells and reflects a minor role of NK cells in the natural HPV life cycle within the epidermis.…”

Section: Discussionmentioning

confidence: 99%

CD56-positive lymphocyte infiltration in relation to human papillomavirus association and prognostic significance in oropharyngeal squamous cell carcinoma

et al. 2016

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Human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx (OSCC) are clinical and biological distinct from their HPV-unrelated counterparts. Patients with HPV-related OSCC display improved prognosis and therefore we investigated possible immune cell infiltrations associated with this tumor phenotype. We retrospectively analyzed a randomly selected cohort of 140 OSCC for presence of immune cells and HPV by immunohistochemistry and PCR followed by beadbased hybridization (Luminex technology). HPV prevalence was 24.3% as determined by positive staining of p16INK4a and detection of high risk HPV-DNA. We found significantly higher numbers of CD56 positive (CD561) cells in tumor and surrounding microenvironment in HPV-associated compared to HPV-negative OSCC (t-test: p 5 0.004 and p 5 0.002). For the entire cohort presence of CD561 cells was associated with increased overall survival independent from HPV (Kaplan-Meier: p 5 0.002; Cox regression: p 5 0.042). Presence of CD561 cells also correlated with a better outcome in HPV-negative and especially in HPV-negative OSCC with alcohol consumption 2 standard drinks per day (Kaplan-Meier: p 5 0.05 and p 5 0.003). Immunofluorescence localization of granular Granzyme B (GZMB) within CD561 cells and coexpression of CD16 and CD56 suggests that detected CD561 cells mainly represent cytotoxic Natural Killer (NK) cells. The fraction of potentially cytotoxic NK cells was significantly higher in HPV-associated compared to HPV-negative OSCC (Mann-Whitney-U-Test: p 5 0.011). The elevated abundance and activity of cytotoxic NK cells in OSCC with HPV driven carcinogenesis might contribute to favorable outcome in HPV-related OSCC.Head and neck cancer (HNC, comprising cancers of the oral cavity, lip, pharynx, nasopharynx and larynx) is ranking at position seven of newly diagnosed cancers and cause of cancer death worldwide, with 4.8% of total cancer incidence and 4.6% of total cancer mortality. 1 In particular oropharyngeal squamous cell carcinomas (OSCC) are related to high risk human papillomavirus (HPV) infection, which is accepted to be causally connected to HNC. 2,3 A recently published metaanalysis demonstrates a rising incidence of HPV1 OSCC in the United States from 21% (pre-1990), to 51% (1990-1999), to 65% (2000-2013). 4 Patients with HPV-associated OSCC show lower levels of disease recurrence and progression compared to patients with HPV-negative OSCC. Even with good loco regional tumor control, patients with HPV-associated OSCC have similar rates of distant metastases as patients with HPVnegative OSCC. Further efforts are needed to understand clinical and biological features of this distinct disease. 2,5,6 Molecular basis of HPV-associated cancers differ from their HPVunrelated counterparts. 3 Pathways related to cell cycle control or apoptosis (commonly affected by mutations in HPVnegative cancers) are silenced at protein level by HPVoncoproteins (mainly E6 and E7). It has been speculated that lower levels of genetic alterations contribute to better treat...

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“…E5, E6 and E7 proteins are considered to be associated with virus immune evasion. The product of E5 could downregulate the histocompatibility leucocyte antigen (HLA) expression of the infected cells, facilitating virus immune escape (13,14). E6 and E7 are considered as tumorigenic genes; their products could bind to tumor suppressor protein p53 and arrest cell cycle, impairing the infected cells apoptosis and enhancing their transformation (15).…”

Section: Effect Of Human Papillomavirus Infection On the Immune Systementioning

confidence: 99%

Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer

et al. 2015

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Abstract. Human papillomavirus (HPV) is widely known as a cause of cervical intraepithelial neoplasia (CIN) and cervical cancer. The mechanisms involved have been studied by numerous studies. The integration of the virus genome into the host cells results in the abnormal regulation of cell cycle control. HPV can also induce immune evasion of the infected cells, which enable the virus to be undetectable for long periods of time. The induction of immunotolerance of the host's immune system by the persistent infection of HPV is one of the most important mechanisms for cervical lesions. The present review elaborates on the roles of several types of immune cells, such as macrophages and natural killer cells, which are classified as innate immune cells, and dendritic cells (DCs), cluster of differentiation (CD)4 + /CD8 + T cells and regulatory T cells, which are classified as adaptive immune cells. HPV infection could effect the differentiation of these immune cells in a unique way, resulting in the host's immune tolerance to the infection. The immune system modifications induced by HPV infection include tumor-associated macrophage differentiation, a compromised cellular immune response, an abnormal imbalance between type 1 T-helper cells (Th1) and Th2 cells, regulatory T cell infiltration, and downregulated DC activation and maturation. To date, numerous types of preventative vaccines have been created to slow down carcinogenesis. Immune response activation-based therapeutic vaccine is becoming more and more attractive for the treatment of HPV-associated diseases.

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HPV-16 E5 down-regulates expression of surface HLA class I and reduces recognition by CD8 T cells

Cited by 137 publications

References 26 publications

Intraperitoneal Oxidative Stress in Rabbits with Papillomavirus-Associated Head and Neck Cancer Induces Tumoricidal Immune Response That Is Adoptively Transferable

Intraperitoneal Oxidative Stress in Rabbits with Papillomavirus-Associated Head and Neck Cancer Induces Tumoricidal Immune Response That Is Adoptively Transferable

CD56-positive lymphocyte infiltration in relation to human papillomavirus association and prognostic significance in oropharyngeal squamous cell carcinoma

Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer

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