Association between Toll-like Receptor and Tumor Necrosis Factor Immunological Pathways in Uterine Cervical Neoplasms

Abstract

Introduction The immune system plays a critical role in the defense against human papillomavirus (HPV) infection and its persistence. Toll-like receptors (TLRs) are membrane receptors responsible for activation of the innate immune response, and an association between TLR expression and uterine cervical cancer has been shown. Tumor necrosis factors (TNFs) are among the main mediators of skin and mucosa inflammation. The aim of this study was to demonstrate the association between TLR and TNF immune expression and cervical cancer and premalignant cervical lesions. Methods A total of 64 embedded tissues were obtained from gynecological procedures, including 35 specimens with cervical intraepithelial neoplasia (CIN) and 10 specimens with cervical squamous cell carcinoma (CSCC) as well as 19 normal cervical samples. The expression of TLR2, TLR3, TLR4, TNF-α and TNF-β was measured by immunohistochemistry and graded into low and high levels of expression. Results There was an association between the expression levels of TLR2 and those of TNF-α and TNF-β (p = 0.01 and p = 0.021, respectively) in the cervical cancer and CIN groups. TLR4 expression was associated with TNF-α and TNF-β expression (p = 0.016 and p = 0.025, respectively) in these 2 groups. By contrast, TLR3 was not statistically associated with TNF-α or TNF-β in any of the groups. Conclusions There might be an association of the TLR2 and TLR4 pathways with the immunological response of TNF-α and TNF-β in cervical cancer. These markers are also expressed at higher levels in cervical cancer and premalignant lesions compared to normal controls.

Expression and clinical significance of SATB1 and TLR4 in breast cancer

“…In our study, we found that TLR4 was positively expressed in 58.33% cases of breast cancer tissues and in 90.57% cases of adjacent non-cancerous tissue. The positive expression rate of TLR4 in this study is consistent with previous studies ( 35 , 36 ). We also found that TLR4 expression was not significantly correlated with age, menopause, or the expression of the PR and HER-2 proteins.…”

“…TLR4 can mediate MyD88-dependent pathways through the interaction with a series of cytokines to promote tumorigenesis ( 31 ). Clinical studies also found that TLR4 was correlated with the growth and metastasis of gastric cancer ( 32 ), ovarian cancer ( 33 , 34 ), cervical cancer ( 35 ), and other types of tumor cells. In our study, we found that TLR4 was positively expressed in 58.33% cases of breast cancer tissues and in 90.57% cases of adjacent non-cancerous tissue.…”

HPV Induces Changes in Innate Immune and Adhesion Molecule Markers in Cervical Mucosa With Potential Impact on HIV Infection

“…in the cervix, data in the literature are controversial, with some groups detecting an increase (45,46) and others a reduction (42) during HPV infection or cancer development. Herein, no differences in TLR4 expression were found between HPV-and HPV+ cervical samples.…”

The role of TLRs in cervical cancer with HPV infection: a review

“…Furthermore, tumor development often is associated with abnormal expression of TLRs and chronic inflammation, yet the exact mechanism is not clear. de Matos et al 35 found that the expression levels of TLR2 and TLR4 were higher in cervical cancer and premalignant lesions compared to normal controls. Studies also found that TLRs, especially TLR4, TLR5 and TLR9, are closely related to HPV infection and cervical cancer.…”