PD-1 + CD8 + TILs and CD57 + CD8 + TALs are associated with Prognosis of Patients with Advanced HGSOC

Objective: Programmed cell death protein-1 (PD-1) expression is associated with activation and exhaustion of CD8 + T-cells, and CD57 is a marker of senescence. The impact of PD-1 + CD8 + T-cells and CD57 + CD8 + T-cells on the prognosis of patients with advanced high-grade serous ovarian cancer (HGSOC) is unclear. Methods The percentage of PD-1 + and CD57 + among CD8 + T-cells was assessed by flow cytometry in tumor-infiltrating lymphocytes (TILs, n = 67) and tumor ascites lymphocytes (TALs, n = 74). To better stratify the survival risk, the optimal cutoff for the frequency of PD-1 + and CD57 + in CD8 + TILs and CD8 + TALs were obtained by the log-rank maximization method. Proliferation and functional properties of PD-1 + CD8 + T-cells and CD57 + CD8 + T-cells were assessed in vitro. Results Patients with higher PD-1 + CD8 + TILs (> 87.8%) have longer platinum-free interval (PFI) and overall survival (OS). Patients with higher CD57 + CD8 + TALs (> 32.66%) are more likely to be resistant to chemotherapy and have lower complete remission rates, shorter PFI and OS. Multivariate analysis showed that the composite score of PD-1 + CD8 + TILs and CD57 + CD8 + TALs was an independent prognostic factor. The status of PD-1 + CD8 + TILs and CD57 + CD8 + TALs was significantly associated with tumor microenvironment specific immunophenotypes. PD-1 + CD8 + TILs were still in a precursor exhaustion state with stem cell properties and high proliferative ability. CD57 + CD8 + TALs exhibited senescence features, with impaired proliferation ability and secreted superfluous pro-inflammatory cytokines that aggravate immunosuppression. Conclusions This study suggests the potential of PD-1 + CD8 + TILs and CD57 + CD8 + TALs at diagnosis as prognostic biomarkers in advanced HGSOC.