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
摘要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.
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