Cytokine expression profiles in cervical mucus from patients with cervical cancer and its precursor lesions

Sayaka Otani, Takuma Fujii, Iwao Kukimoto, Naoki Yamamoto, Tetsuya Tsukamoto, Ryoko Ichikawa, Eiji Nishio, Aya Iwata

Research output: Contribution to journalArticle

Abstract

Human papillomavirus (HPV) infection can persist in the cervical epithelium without provoking a strong host immune response, leading to the development of cervical cancer. Cytokines, which mediate innate and adaptive immune activities, are secreted in the cervical mucus; however, there is currently no appropriate method for assessing cytokine levels in mucus specimens. Here, we employed multiplexed bead-based immunoassays to examine cytokine levels in cervical mucus using both weighted-volume and total protein concentration methods to adjust for different specimen volumes in individual patients. Out of 18 cytokines initially examined in the primary cohort patient group (n = 28), 14 were detected in more than 10% of the samples. Of these 14 cytokines, expression levels of interferon (IFN)-γ, granulocyte–macrophage colony-stimulating factor (GM-CSF), RANTES, and eotaxin were significantly increased with the disease severity in the secondary cohort patient group (n = 235). We also examined associations between cytokine levels and clinical parameters, such as cytology and HPV genotype. Of the 14 cytokines, granulocyte colony-stimulating factor (G-CSF) was downregulated in HPV-positive specimens. Examination of co-expression patterns of cytokines in relation to HPV infection status revealed that several pairs of cytokines were simultaneously upregulated in HPV-positive cases, including INF-γ and interleukin (IL)-17A, GM-CSF and monocyte chemoattractant protein-1 (MCP-1), GM-CSF and RANTES, IL-17A and RANTES, and MCP-1 and eotaxin. Interestingly, upregulation of GM-CSF and RANTES might reflect a shift in immuno-regulatory cytokines in HPV-positive specimens, potentially associated with more severe cervical neoplasia.

Original languageEnglish
Pages (from-to)210-219
Number of pages10
JournalCytokine
Volume120
DOIs
Publication statusPublished - 08-2019

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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    Otani, S., Fujii, T., Kukimoto, I., Yamamoto, N., Tsukamoto, T., Ichikawa, R., Nishio, E., & Iwata, A. (2019). Cytokine expression profiles in cervical mucus from patients with cervical cancer and its precursor lesions. Cytokine, 120, 210-219. https://doi.org/10.1016/j.cyto.2019.05.011