Th17 response in patients with cervical cancer

Abstract

Persistent infection by high-risk human papillomavirus (HR-HPV) is the main risk factor for uterine cervical cancer (UCC). However, viral infection alone is not sufficient for the development and progression of premalignant cervical lesions for cancer. In previous years it has been suggested that the adaptive immune response triggered by the differentiation of naïve helper T cells in Th17 cells may serve an important role in disease development. It has been hypothesized that Th17 cells may be involved in the promotion of UCC, as high levels of interleukin 17 (IL17) expression have been detected in the mucosa of the uterine cervix of patients affected by the disease. However, the role of Th17 cells in the tumor development and progression remains unclear. It is believed that the immune response of the Th17 type during persistent infection of the genital tract with HR-HPV triggers chronic inflammation with a long duration with the production of IL17 and other pro-inflammatory cytokines, creating a favorable environment for tumor development. These cytokines are produced by immune system cells in addition to tumor cells and appear to function by modulating the host immune system, resulting in an immunosuppressive response as opposed to inducing an effective protective immune response, thus contributing to the growth and progression of the tumor. In the present review, the latest advances are presented about the function of Th17 cells and the cytokines produced by them in the development and progression of UCC.

Keywords: Th17 cells; carcinogenesis; immune system; uterine cervical cancer.

Figure 1.

Representative scheme summarizing the mechanisms and cytokines involved in the differentiation process of Th0 in Th17 cells, and the potential function of these cells in tumor progression. APC, antigen-presenting cell; p-STAT, phosphorylated signal transducer and activator of transcription; IL, interleukin; TGF-β, tumor growth factor β; Th, T helper cell; VEGF, vascular endothelial growth factor; PGE2, prostaglandin E2; NO, nitric oxide; Th0, CD4⁺ T cells.

Figure 2.

Representative scheme proposed for summarizing the function of different cell types, mechanisms and cytokines involved in the plasticity process and reciprocity in the conversion of Th1, Th17 and Treg cells for a better understanding of the ambiguous functions of the Th17 cells in the clinical course of a tumor, which may contribute to the regression or progression of a tumor. APC, antigen-presenting cell; p-STAT, phosphorylated signal transducer and activator of transcription; IL, interleukin; TGF-β, tumor growth factor β; Th, T helper cell; IDO, indoleamine 2,3-dioxygenase; DCS, dendritic cells; Treg, T regulatory cells; IFN-γ, type II interferon.