Correlation of CXCL12 Expression and FoxP3+ Cell Infiltration with Human Papillomavirus Infection and Clinicopathological Progression of Cervical Cancer

Abstract

Human cervical cancer is an immunogenic tumor with a defined pattern of histopathological and clinical progression. Tumor-infiltrating T cells contribute to immune control of this tumor; however, cervical cancer dysregulates this immune response both through its association with human papillomavirus (HPV) infection and by producing cytokines and chemokines. Animal tumor models have revealed associations between overproduction of the chemokine stromal cell-derived factor-1 (SDF-1 or CXCL12) and dysregulation of tumor-specific immunity. We therefore proposed that CXCL12 expression by cervical precancerous and cancerous lesions correlates with histopathological progression, loss of immune control of the tumor, and HPV infection. We found a significant association between cancer stage and CXCL12 expression for squamous and glandular lesions as well as with the HPV16؉ (high-risk) status of the neoplastic lesions. Cancer progression was correlated with increasing levels of FoxP3 T-cell infiltration in the tumor.

FOXP3 autoantibody as a potential early prognostic serum biomarker in patients with cervical cancer

“…Therefore, the population of FOXP3 + T cells was significantly higher in patients with cervical cancer than in healthy subjects. Jaafar et al [33] found that in animal models, cytokine overexpression in cervical cancer contributed to the accumulation of FOXP3 + T cells. Further studies reported that FOXP3 expression was changed in benign and malignant cervical lesions.…”

Premetastatic milieu explained by TLR4 agonist-mediated homeostatic inflammation

“…22 Correlation between Treg infiltration and CXCL12 expression has been found in cervical cancer. 23 Classical Tregs inhibit T cells in lymphoid organs. Although CXCL12 is expressed in bone marrow, G-CSF has been reported to reduce CXCL12 in bone marrow.…”

G801A Polymorphism of Human Stromal Cell-Derived Factor 1 Gene Raises No Susceptibility to Neoplastic Lesions of Uterine Cervix

“…4 The expression of this chemokine SDF-1 was reported to be significantly increased in cervical epithelium as the neoplastic lesions progressed from preinvasive to invasive cancer. 5 In the other way, the expression of chemokine receptor 4 (CXCR4), which acts as receptor to SDF-1, could be detected in most primary tumors, and its strong expression in the primary tumor was associated with metastatic spread to pelvic nodes, whereas normal cervical epithelium was detected negative for the expression of SDF-1 and its receptor CXCR4. In addition, SDF-1 expression was reported to be directly correlated with known determinants of immune dysregulation, such as HPV infection itself and regulatory T-cell infiltration.…”