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

Abstract 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.