Role of Regulatory B Cells in the Progression of Cervical Cancer

Mediators Inflamm. 2019 Jun 18:2019:6519427. doi: 10.1155/2019/6519427. eCollection 2019.

Abstract

This study is to investigate the role of regulatory B (Breg) cells in cervical cancer. In total, 70 cases of cervical cancer, 52 cases of cervical intraepithelial neoplasia (CIN), and 40 normal controls were enrolled. The percentage of Breg cells was detected by flow cytometry. Serum levels of IL-10 were measured by ELISA. The correlation between Breg cells and the clinical characterizations of cervical cancer was analyzed. The inhibition effect of Breg cells on CD8+ T cells was tested by blocking IL-10 in vitro. The percentage of CD19+CD5+CD1d+ Breg cells and the level of IL-10 of patients with cervical cancer or CIN were significantly higher than those in the control group (P < 0.05). And the postoperative levels of Breg cells and IL-10 were significantly lower than the preoperative levels (P < 0.05). Breg cells and the IL-10 level were positively correlated in cervical cancer patients (r = 0.516). In addition, the Breg cell percentage was closely related to the FIGO stages, lymph node metastasis, tumor differentiation, HPV infection, and the tumor metastasis of cervical cancer (P < 0.05). The Breg cell percentage was negatively correlated with CD8+ T cells of cervical cancer patients (r = -0.669). The level of IL-10 in the culture supernatant of Bregs treated with CpG was significantly higher than that of non-Bregs (P < 0.05). After coculture with Bregs, the quantity of CD8+ T cells to secrete perforin and Granzyme B was significantly decreased, and this effect was reversed after blocking IL-10 by a specific antibody. Breg cells are elevated in cervical cancer and associated with disease progression and metastasis. Moreover, they can inhibit the cytotoxicity of CD8+ T cells.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD19 / blood
  • Antigens, CD1d / blood
  • B-Lymphocytes, Regulatory / immunology*
  • CD5 Antigens / blood
  • CD8-Positive T-Lymphocytes / cytology
  • Case-Control Studies
  • CpG Islands
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Granzymes / metabolism
  • Humans
  • Interleukin-10 / blood
  • Lymphatic Metastasis
  • Middle Aged
  • Perforin / metabolism
  • Uterine Cervical Dysplasia / immunology*
  • Uterine Cervical Neoplasms / immunology*

Substances

  • Antigens, CD19
  • Antigens, CD1d
  • CD19 molecule, human
  • CD1D protein, human
  • CD5 Antigens
  • IL10 protein, human
  • PRF1 protein, human
  • Perforin
  • Interleukin-10
  • Granzymes