Distribution and functions of γδ T cells infiltrated in the ovarian cancer microenvironment

J Transl Med. 2019 May 7;17(1):144. doi: 10.1186/s12967-019-1897-0.

Abstract

Background: The role of γδ T cells, innate-like lymphocytes with unrestrained MHC, in various malignancies has recently been extensively studied. However, there is limited research regarding γδ T cells in ovarian cancer (OC) patients.

Methods: Here, we investigated the distribution patterns of γδ T cells and their main subsets in peripheral blood and tumor tissues among OC patients, benign ovarian tumor (BOT) patients, and age-matched healthy controls (HC) by flow cytometry, as well as the expression levels of IFN-γ and IL-17A secreted from γδ T cells. Immunohistochemical staining was utilized to detect the numbers of γδ T cells and their main subsets in different types of ovarian tumor tissues. Additionally, we also investigated chemotaxis effects on γδ T cells, as well as their cytotoxic activity and proliferation.

Results: We found that the percentages of γδ T cells and Vδ1 T cells were significantly higher in OC tissues than BOT tissues and normal (N) ovarian tissues, while there were no obvious differences in peripheral blood. Meanwhile, higher numbers of γδ T cells and Vδ1 T cells were observed in OC tissues, and were positively related to advanced clinicopathological features of OC patients. Further, the levels of IFN-γ secreted by γδ T cells were relatively lower, while IL-17A was expressed at a high level in both the peripheral blood and tissues of OC patients. Chemotaxis assay revealed that supernatants derived from OC tissues possessed a stronger capacity to attract and recruit γδ T cells. However, γδ T cells sorted from OC tissues showed weakened cytotoxic activity against ovarian cancer cells, and γδ T cells cocultured with OC tissue supernatants could effectively inhibit the proliferative activity of naïve CD4+ T cells.

Conclusions: These data suggested that γδ T cells might have critical roles in OC progression and potential utilization in treatment approaches or prognosis prediction.

Keywords: Cytotoxicity capacity; Immunosuppressive activity; Ovarian cancer; Vδ1 T cell; Γδ T cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cytotoxicity, Immunologic
  • Female
  • Humans
  • Immunosuppression Therapy
  • Interleukin-17 / metabolism
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Middle Aged
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / pathology
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Tumor Microenvironment / immunology*

Substances

  • IL17A protein, human
  • Interleukin-17
  • Receptors, Antigen, T-Cell, gamma-delta