Composite score of PD-1 + CD8 + tumor-infiltrating lymphocytes and CD57 + CD8 + tumor ascites lymphocytes is associated with prognosis and tumor immune microenvironment of patients with advanced high-grade serous ovarian cancer.

Abstract

Objective: The expression of programmed death 1 (PD-1) on CD8⁺ T cells is associated with their activation and exhaustion, while CD57 serves as a senescence marker. The impact of PD-1⁺ and CD57⁺CD8⁺ T cells on the prognosis of patients with advanced high-grade serous ovarian cancer (HGSOC) remain unclear.

Methods: We assessed the percentages of PD-1⁺ and CD57⁺CD8⁺ T cells in tumor-infiltrating lymphocytes (TILs, n=85) and tumor ascites lymphocytes (TALs, n=87) using flow cytometry. The optimal cutoffs for these markers in TILs and TALs were determined through the log-rank maximization method. Gene expression analysis elucidated the tumor immune microenvironment (TIME, n=36).

Results: Patients with higher PD-1⁺CD8⁺ TILs (>87.8%) exhibited longer platinum-free interval (PFI) and overall survival (OS). In contrast, those with elevated CD57⁺CD8⁺ TALs (>28.69%) were more likely to experience chemotherapy and had lower complete remission rates, shorter PFI and OS. PD-1⁺CD8⁺ TILs are primarily displayed an effector memory state with strong proliferative and secretory capabilities. Approximately 50% of CD57⁺CD8⁺ TALs were terminally differentiated, exhibiting significantly impaired proliferation. Based on the proportions of PD-1⁺CD8⁺ TILs and CD57⁺CD8⁺ TALs, patients were categorized into good, median and poor prognosis groups, with median PFI of 47.78, 27.29 and 11.96 months, respectively (P<0.0001). Median OS for these groups was not reach, 49.23 and 30.92 months, respectively (P<0.0001). Patients with poor prognosis exhibit significantly reduced CD8⁺ T cell proportion and increased M2 macrophage in the TIME, alongside downregulation of multiple T cell activation-related pathways.

Conclusions: Lower levels of PD-1⁺CD8⁺ TILs and higher CD57⁺CD8⁺ TALs, assessed prior to treatment, correlated with poor prognosis and suppressive TIME in advanced HGSOC.