Immune evasion in human papillomavirus-associated cervical cancer

Tindle, Robert W.

doi:10.1038/nrc700

Cited by 350 publications

(311 citation statements)

References 42 publications

Supporting

Mentioning

290

Contrasting

Unclassified

Order By: Relevance

“…E7 protein expression in keratinocytes alters expression of genes that influence the host resistance to infection and immune function, leading to peripheral tolerance within the CTL population. 30 Tindle 30 assumes that successful therapeutic vaccination has to take into account how E7 evades the immune response and has to overcome the E7-tolerogenic status of the patient. One possibility might be to combine the activation of CTLs by E7 with the induction of an inflamma- tory environment, which thereby provides signal to turn immature, tolerizing DCs into mature, activating DCs.…”

Section: Discussionmentioning

confidence: 99%

Transcutaneous immunization in mice: Induction of T-helper and cytotoxic T lymphocyte responses and protection against human papillomavirus-induced tumors

2006

View full text Add to dashboard Cite

Previous reports have shown that transcutaneous immunization (TCI) with proteins or peptides in combination with adjuvants efficiently induces specific cellular and humoral immune responses. However, depending on the kind of skin pretreatment, induction of cellular immune responses was restricted to generation of either specific cytotoxic T lymphocytes (CTLs) or T-helper (Th) cells. In this study, we induced antigen-specific CTL responses together with the appropriate Th responses by TCI of C57BL/6 mice. We applied ovalbumin protein or an ovalbuminderived fusion peptide containing a CTL and Th epitope together with a combination of cholera toxin (CT) and CpG oligodeoxynucleotide (CpG) onto cold wax-depilated and hydrated bare skin. TCI with the ovalbumin fusion peptide induced more robust CTL and Th responses than that with ovalbumin protein. The fusion peptide in combination with the nontoxic CT derivative CTA1-D2D1 and CpG induced an antigen-specific CTL response, albeit less efficiently than in combination with complete CT. Further, we compared the potency of HPV-16 E7 oncoprotein-derived peptides containing single (CTL) or multiple (CTL 1 Th 1 B cell) epitopes to induce effective CTL responses. Strong E7-specific CTL responses were detected only after TCI with the E7 multiepitope peptide. This peptide was also shown to protect mice against tumor growth after challenge with HPV-16 E7-positive tumor cells. TCI with E7 protein and CT/CpG led to formation of an E7-specific humoral immune response. ' 2005 Wiley-Liss, Inc.Key words: transcutaneous immunization; human papillomavirus type 16 E7 (HPV-16 E7); CTA1-D2D1; cytotoxic T lymphocyte; T helper cell; ovalbumin; tumor protection TCI is a novel strategy in modern vaccinology. By this application, blood-borne transmission of diseases through the reuse of needles, which is a common practice in remote parts of the world, can be circumvented and better compliance of vaccinees obtained. Apart from its benefits toward vaccine safety, TCI targets LCs, a dense population of highly accessible APCs within the skin. 1 An important feature of vaccination against viral infections and virus-based tumors is the induction of CTLs. 2-4 Upon activation by APCs, predominantly DCs, CTLs are able to selectively kill antigen-expressing cells. 5 For clearance of certain viral infections, the aid of Th cells for CTL activation is necessary. 6 The bias to one of the 2 Th subsets (Th1 > Th2) is a prerequisite for specific CTL induction. 7 Generation of specific CTLs against proteinaceous or peptidebased vaccines in combination with adjuvants after TS of the skin is possible. 8-10 TS leads to removal of the outermost horny layer of the skin, resulting in enhanced permeability and maturation and activation of LCs via inflammatory cytokines secreted from keratinocytes. 11,12 The barrier function of the SC can also be bypassed by hydration of the skin, which leads to swelling of the keratinocytes and pooling of fluid into intercellular spaces. This kind of pretreatment of the skin leads to ...

show abstract

Section: Discussionmentioning

confidence: 99%

Transcutaneous immunization in mice: Induction of T-helper and cytotoxic T lymphocyte responses and protection against human papillomavirus-induced tumors

2006

View full text Add to dashboard Cite

show abstract

“…HPV is spreading through sexual contact; Studies point out that 30-60% of all sexually active adults acquire HPV during their reproductive lives (Tindle, 2002) and it is suspected to be higher in younger women comparing to older women (Smith et al, 2008). Fortunately more than 80% of HPV infections are removed over a 3-4 years without any intervention; on the other hand primary prevention trough vaccination and screening for cervical cancer seems to be effective (Wong, 2009).…”

Section: Introductionmentioning

confidence: 99%

Knowledge and Attitude of Iranian University Students toward Human Papilloma Virus

Ghojazadeh

Azar²,

Saleh³

et al. 2012

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Introduction: Increasing prevalence of human papilloma virus (HPV) infection and its association with cervical cancer as a leading cause of death make it necessary to evaluate and improve the public knowledge, especially of university students, about this cause of disease. Methods: A cross-sectional study of knowledge and attitude of a total 669 students from Tabriz University of Medical Sciences was therefore performed with a modified validated questionnaire, arranged into 5 parts and containing 55 questions, in July 2011. Questions were directed to study socio-demographic characteristics of the participant, knowledge about HPV disease, transmission route, relationship with cervical cancer, predisposing factors, and participants attitude toward people with HPV infection. Results: All of the participants were Moslem with a mean age 25.6±5.33 years of age. All of the participants had heard of HPV, and acquired their knowledge through university courses (90.6%); the majority of them knew that HPV is a sexually transmitted disease and a potential cause for genital warts but general knowledge about details was not high. Mean knowledge score of residents and post graduate midwifery and nursing students was high as compared to other groups (P<0.001). Statements that indicated the presence of fear to communicate with people suffering HPV and people's avoidance to rely on babysitting of these patients were observed. Educational level (β=0.21, P<0.001), age (β=0.18, P=0.002,) and smoking (β=-0.11, P=0.006) were predicted to effect knowledge. Conclusions: Moderate level of knowledge about HPV among medical university students makes it necessary to set effective national public health efforts on HPV education and prevention considering he excess of young population in Iran vulnerable to cervical cancer.

show abstract

“…Hence, cancer of the cervix uteri is the final outcome of a long term selection and escape process, where HPV positive cells are no longer controlled by immunological surveillance. 2 Consequently, a physiological intact communication route between inflammatory and HPV-containing cells is an indispensable prerequisite for a proper antiviral response. 3 Targeting IFN-signaling actually provides a general selective advantage for tumor formation, because it favors the disruption of the intercellular cross-talk between HPV positive and immunological effector cells.…”

mentioning

confidence: 99%

Genetic redundancy in human cervical carcinoma cells: Identification of cells with “normal” properties

Bachmann

Zawatzky

Rösl

2007

Intl Journal of Cancer

View full text Add to dashboard Cite

Although it is generally assumed that cancer arises from a singular cell, a tumor must be considered as a dynamic and emergent biological structure, whose organizing principle is determined by genetic and epigenetic modifications, occurring variably in response to microenvironmental selection conditions. As previously shown, HPV-positive cervical carcinoma cells have lost their ability to induce IFN-b upon TNF-a treatment. However, regarding cancer as a non-linear system, which may, even in the absence of an apparent selection pressure, fluctuate between different ''metastable'' phenotypes, we demonstrate that TNF-a mediated IFN-b induction is not irreversibly disturbed in all cells. Using the IFN-b sensitive Encephalomyocarditis virus (EMCV) as a tool to monitor antiviral activity in long-term established malignant HeLa cells, rare IFN-b expressing clones were rescued from a population of non-responsive and EMCV-sensitive cells. Antiviral activity was mediated by the re-expression of IRF-1 and p48 (IRF-9), both key regulatory molecules normally found to be suppressed in cervical carcinoma cells. Upon inoculating of selected clones into immunocompromised animals, a reduced or even an absence of tumorigenicity of initially highly malignant cells could be discerned. These data indicate that both the absence of interferon signaling and the ability to form tumors were reversed in a minority of cells. We provide a paradigm for the existence of innate genetic redundancy mechanisms, where a particular phenotype persists and can be isolated without application of drugs generally changing the epigenetic context. ' 2007 Wiley-Liss, Inc.Key words: human papillomaviruses; interferon-b regulation; EMCVcytolysis; tumor necrosis factor alpha; redundancy mechanisms; oscillation; chaotic cell systems; tumorigenicity Infections with certain types of human papillomaviruses (HPV) are the major cause for the development of cervical cancer. 1 Epidemiological studies show that immunodeficient women have a significantly higher risk of developing a tumor than age-matched controls. Hence, cancer of the cervix uteri is the final outcome of a long term selection and escape process, where HPV positive cells are no longer controlled by immunological surveillance. 2 Consequently, a physiological intact communication route between inflammatory and HPV-containing cells is an indispensable prerequisite for a proper antiviral response. 3 Targeting IFN-signaling actually provides a general selective advantage for tumor formation, because it favors the disruption of the intercellular cross-talk between HPV positive and immunological effector cells. 4 In a previous investigation, we demonstrated that the antiviral effect of TNF-a, which is mediated by IFN-b gene activation, 5 is disturbed in HPV positive cervical carcinoma cells. 6 The reason for this failure is the lack of interferon-regulatory factor (IRF)-1 and p48 (IRF-9) expression, two key regulators, tightly involved in the transcriptional control of the intermediate and the delayed interfero...

show abstract

Immune evasion in human papillomavirus-associated cervical cancer

Cited by 350 publications

References 42 publications

Transcutaneous immunization in mice: Induction of T-helper and cytotoxic T lymphocyte responses and protection against human papillomavirus-induced tumors

Transcutaneous immunization in mice: Induction of T-helper and cytotoxic T lymphocyte responses and protection against human papillomavirus-induced tumors

Knowledge and Attitude of Iranian University Students toward Human Papilloma Virus

Genetic redundancy in human cervical carcinoma cells: Identification of cells with “normal” properties

Contact Info

Product

Resources

About