Clinical significance of CD38 and CD101 expression in PD-1+CD8+ T cells in patients with epithelial ovarian cancer

Oncol Lett. 2020 Jul;20(1):724-732. doi: 10.3892/ol.2020.11580. Epub 2020 Apr 28.


Previous studies using mouse liver tumor models have indicated that coexpression of CD38 and CD101 in programmed cell death-1 (PD-1)+CD8+ T cells may reflect fixed dysregulation of CD8+ T cells and thus indicate a poor response to anti-PD-1 immunotherapy. However, whether CD38 and CD101 expression in PD-1+CD8+ T cells can predict the clinical status and efficacy of chemotherapy for various cancer types, including ovarian cancer (OC), remains unclear. In the present study, peripheral blood mononuclear cells (PBMCs) were obtained by Ficoll-Hypaque gradient centrifugation from 96 fresh samples from healthy adult volunteers and patients with epithelial OC, aged 55.21±9.91 years. Additionally, tumor-infiltrating lymphocytes (TILs) were separated using a combination of mechanical, chemical and enzymatic digestion from fresh surgically removed tumor tissues from 15 patients with epithelial OC. The expression of CD38 and CD101 in PD-1+CD8+ T cells or TILs was detected by flow cytometry or immunofluorescence (IF) staining, respectively. The association between the level of CD38/CD101 expression and clinicopathological parameters or postoperative chemotherapy in patients with OC was statistically analyzed. The levels of CD38/CD101-coexpressing PD-1+CD8+ T cells were significantly increased in PBMCs and TILs of patients with OC compared with those of healthy volunteers. The frequency of PD-1+CD38+CD101+CD8+ T cells among the total PD-1+CD8+ T cell subpopulation was negatively associated with clinical stage, lymph node metastasis and postoperative chemotherapy prognosis in patients with OC. Furthermore, IF staining confirmed colocalization of CD38 and CD101 on the majority of TILs in OC tissues. Thus, the present study suggests that coexpression of CD38 and CD101 in peripheral PD-1+CD8+ T cells and TILs may serve as a new indicator for diagnosis and treatment efficacy in patients with epithelial OC.

Keywords: CD101; CD38; diagnosis; ovarian cancer; programmed cell death-1; tumor-infiltrating lymphocytes.