An association of iNKT+/CD3+/CD161+ lymphocytes in ovarian cancer tissue with CA125 serum concentration

Immunobiology. 2020 Nov;225(6):152010. doi: 10.1016/j.imbio.2020.152010. Epub 2020 Aug 28.

Abstract

The purpose of this study was to investigate the association of iNKT (human invariant natural killer T) cells with the key marker of ovarian cancer (OC) - CA125 (cancer antigen125) in serum. The study reports the assessment of iNKT cells in peripheral blood and tissue of benign and borderline ovarian tumors (BOTs) and in the advanced-stage ovarian cancer. The study groups were as follows: 25 women with benign ovarian tumors, 11 women with BOTs, and 24 women with primary advanced-stage ovarian cancers. The control group consisted of 20 patients without the ovarian pathology. The rates of iNKT lymphocytes in the peripheral blood and tissue specimens were evaluated by a flow cytometry. Significant differences in the percentage of iNKT+/CD3+ of CD3+ lymphocytes, iNKT+/CD3+/CD161+ among CD3+ and iNKT+/CD3+/CD161+ among CD3+/iNKT+ between the control group and patients with ovarian tumors in the peripheral blood and tumor tissue were identified. Significant correlations were noticed between the proportion of lymphocytes iNKT+/CD3+/CD161+ among CD3+/iNKT cells in blood and in cancer tissue of both benign and malignant tumors. In the OC group, neither the ratio of iNKT cells in the blood (P = 0.07), nor the intra-tumor NKT-cell infiltration (P = 0.5) were independent prognostic factors for the follow-up. An increased rate of iNKT cells was detected in benign ovarian tumors compared to OCs. In patients with ovarian cancer, a higher rate of iNKT cells in tumor tissue was present related to that noted in the patient's blood. In addition, a correlation was discovered between the CA125 serum marker and NKT cells from the ovarian cancer tissue. This article has for the first time demonstrated a negative relationship between serum levels and NKT lymphocyte count from ovarian tissue. The inflammatory process in ovarian cancer tissue and the potential infiltration of endothelial immune cells, may result in a reduced number of NKT cells in the tumor microenvironment and increased circulation of the CA125 marker. Presented findings underscore new aspects of the iNKT cells involvement in the ovarian cancer development.

Trial registration: ClinicalTrials.gov NCT03779399.

Keywords: Borderline ovarian tumor; Cystadenocarcinoma; Lymphocyte iNKT; Ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CA-125 Antigen / blood*
  • CD3 Complex / metabolism
  • Female
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Lymphocyte Activation / immunology
  • Lymphocyte Count*
  • Membrane Proteins / blood*
  • NK Cell Lectin-Like Receptor Subfamily B / metabolism
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / metabolism*
  • Ovarian Neoplasms / blood*
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / etiology

Substances

  • CA-125 Antigen
  • CD3 Complex
  • KLRB1 protein, human
  • MUC16 protein, human
  • Membrane Proteins
  • NK Cell Lectin-Like Receptor Subfamily B

Associated data

  • ClinicalTrials.gov/NCT03779399