Toll-Like Receptors 7, 8, and 9 Expression and Function in Primary Human Cervical Cancer Langerhans Cells: Evidence of Anergy

Kumar, Manoj; Adurthi, Sreenivas; Ramachandran, Surya; Mukherjee, Geetashree; Joy, Omana; Krishnamurthy, Hanumanthappa; Krishna, Sudhir; Bafna, U. D.; Uma, Devi K.; Jayshree, R. S.

doi:10.1097/igc.0b013e31827a2003

Cited by 11 publications

(11 citation statements)

References 24 publications

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“…For example, E6 oncoprotein induces significant downregulation of β‐interferon (IFN) in keratinocytes, and the reduction in the expression of α‐IFN response genes has been attributed to the presence of E7 [Nees et al, ; Zhou et al, ]. Furthermore, early oncoproteins are associated with diminished levels of molecules necessary for antigen processing and presentation, such as Toll‐like receptor‐9 (TLR9) and the transporter associated with antigen processing (TAP) [Kumar et al, ; Zhou et al, ]. Additionally, HPV persistence and cervical lesion progression are commonly associated with the failure to mount HPV‐specific type 1 T‐helper and cytotoxic T‐cell responses and characterized by changes in the cytokine expression profile from a Th1 to Th2 response and by the increased expression of Interleukin‐10 (IL10) [Woo et al, ].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of sexually transmitted pathogens associated with HPV infection in cervical samples in a Mexican population

et al. 2015

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Cervical cancer development has been mainly associated with persistent human papillomavirus (HPV) infections. However, HPV infection is unlikely to be sufficient to cause cervical cancer, and the contribution of other sexually transmitted infections (STIs) could be the determining factor for cervical lesion-progression. The aim of this study was to estimate the prevalence of STIs associated with HPV-positivity in 201 cervical samples from patients who underwent annual routine gynecological exams. The overall prevalence of STIs was 57.7%, and the most frequent infection was Ureaplasma spp (UP) (39.8%), followed by Gardnerella vaginalis (GV) (25.9%), α-HPV (18.4%), Chlamydia trachomatis (CT) (1.5%), and Mycoplasma genitalium (MG) (0.5%). The highest prevalence rate of multiple non-HPV infections was observed for the age-range 31-40; for papillomavirus infection, the age-range was 21-30. In normal cervical samples, HPV16 was the most prevalent genotype (24.3%), followed by genotypes 58 (13.5%) and 52 (10.8%). Intriguingly, HPV18 was not detected in the study population, and genotypes 52 and 58 were found exclusively in samples with abnormal cytology. Papillomavirus infection with oncogenic types was significantly associated with GV (P = 0.025) and strongly associated with multiple non-HPV pathogens (P = 0.002). The following variables correlated significantly with cytological diagnosis of low-grade squamous intraepithelial lesion (LSIL): GV (P = 0.028), multiple non-HPV infections (P = 0.001), and high-risk HPV positivity (P = 0.001). Epidemiological data from this study will contribute to the molecular detection of sexually transmitted pathogens from screening programs to identify those women who are at risk for developing cervical lesions.

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Section: Introductionmentioning

confidence: 99%

Prevalence of sexually transmitted pathogens associated with HPV infection in cervical samples in a Mexican population

et al. 2015

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“…[17,18] Some TLRs in tumor cells indeed biologically impact on tumor cell growth and survival. For example, TLR5 is highly expressed in breast carcinoma and gastric carcinoma cells, and TLR5 signaling inhibits breast cancer growth, but promotes the proliferation of gastric cancer cells.…”

Section: Resultsmentioning

confidence: 99%

Application potential of toll-like receptors in cancer immunotherapy

Shi

Chen

et al. 2016

Medicine

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Toll-like receptors (TLRs), as the most important pattern recognition receptors in innate immunity, play a pivotal role in inducing immune response through recognition of microbial invaders or specific agonists. Recent studies have suggested that TLRs could serve as important regulators in the development of a variety of cancer. However, increasing evidences have shown that TLRs may display quite opposite outcomes in cancer development. Although several potential therapeutic Toll-like receptor ligands have been found, the mechanism and therapy prospect of TLRs in cancer development has to be further elucidated to accelerate the clinical application. By performing a systematic review of the present findings on TLRs in cancer immunology, we attempted to evaluate the therapeutic potential of TLRs in cancer therapy and elucidate the potential mechanism of cancer progress regulated by TLR signaling and the reported targets on TLRs for clinical application. An electronic databases search was conducted in PubMed, Chinese Scientific Journal Database, and Chinese Biomedical Literature Database from their inception to February 1, 2016. The following keywords were used to search the databases: Toll-like receptors, cancer therapy, therapeutic target, innate immunity. Of 244 studies that were identified, 97 nonrelevant studies were excluded. In total, 147 full-text articles were assessed, and from these, 54 were excluded as they did not provide complete key information. Thus, 93 studies were considered eligible and included in the analysis. According to the data from the included trials, 14 TLR ligands (77.8%) from 82 studies have been demonstrated to display antitumor property in various cancers, whereas 4 ligands (22.2%) from 11 studies promote tumors. Among them, only 3 TLR ligands have been approved for cancer therapy, and 9 ligands were in clinical trials. In addition, the potential mechanism of recently reported targets on TLRs for clinical application was also evaluated in this review. We show that targeting TLRs in cancer immunotherapy is a promising strategy for cancer therapy, and the specific TLR ligands, either alone or combination, exhibit antitumor potential.

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“…A recent report found that Bcl-2, as an inhibitor of apoptosis, had prognostic value in classical Hodgkin lymphoma 20. The predominant regulator of tumor angiogenesis is VEGF, which has become an important target in the development of novel anti-tumor strategies 21-22, although the clinical effectiveness of these new strategies remains to be seen 23. The increased VEGF and Bcl-2 expression reported here suggests that future therapeutic approaches targeting on angiogenesis can be used in cervical cancer patients.…”

Section: Discussionmentioning

confidence: 99%

The Expression of Toll-like Receptor 8 and Its Relationship with VEGF and Bcl-2 in Cervical Cancer

Zhang¹,

Yang²,

Barnie³

et al. 2014

Int. J. Med. Sci.

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BACKGROUND: Cervical cancer is one of the most common cancers in women worldwide, often associated with the infection of human papillomavirus (HPV). Toll-like receptor 8 (TLR8), a pattern recognition receptor, is involved in viral nucleic acid sensing. Recently TLR8 has been shown to be expressed in cancer cells, and it has been suggested that it may help cancer cell growth and tumor development. The objective of this study is to investigate the expression of TLR8 expression and its relationship with Bcl-2 and VEGF in cervical cancer cells.METHODOLOGY/PRINCIPAL: The mRNA expression levels of Bcl-2, VEGF and TLR-7,-8,-9 in newly diagnosed cervical cancer patients were detected by quantitative real-time PCR (qRT- PCR). Epifluorescence microscope was used to determine the presence of TLR8 protein in Hela cells. The cell cycle and apoptosis were analyzed by flow cytometer, and the cell proliferation was measured by MTT assay. Our data showed the increased mRNA levels of TLR8 in human cervical cancer samples as well as in HeLa cells, a cell line derived from a human cervical cancer. In addition, there was a positive correlation between the expression levels of TLR8 and Bcl-2 and VEGF in cervical cancer patients. When Hela cells were treated with TLR8 agonist CL075, the percentage of cells in G2/M +S was remarkably increased, accompanied by increased COX-2, BCL-2 and VEGF mRNA levels.CONCLUSIONS/SIGNIFICANCE: The mRNA expression level of TLR8 in the patients with cervical cancer and Hela cells were up-regulated, it consistent with the increased expression of VEGF and Bcl-2. The results suggest that TLR8 may be an interesting therapeutic target in cervical cancer.

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Toll-Like Receptors 7, 8, and 9 Expression and Function in Primary Human Cervical Cancer Langerhans Cells: Evidence of Anergy

Cited by 11 publications

References 24 publications

Prevalence of sexually transmitted pathogens associated with HPV infection in cervical samples in a Mexican population

Prevalence of sexually transmitted pathogens associated with HPV infection in cervical samples in a Mexican population

Application potential of toll-like receptors in cancer immunotherapy

The Expression of Toll-like Receptor 8 and Its Relationship with VEGF and Bcl-2 in Cervical Cancer

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