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  

作　　者：Tianhui He Jie Zhang Lin Zeng Zhongnan Yin Bo Yu Xi Zhang Xiaoxue Yang Chunliang Shang Lixiang Xue Hongyan Guo 

机构地区：[1]Department of Obstetrics and Gynecology,Peking University Third Hospital,Beijing 100191,China [2]Center of Basic Medical Research,Institute of Medical Innovation and Research,Peking University Third Hospital,Beijing 100191,China [3]Biobank,Peking University Third Hospital,Beijing 100191,China [4]Research Center of Clinical Epidemiology,Peking University Third Hospital,Beijing 100191,China

出　　处：《Chinese Journal of Cancer Research》2025年第1期73-89,共17页中国癌症研究(英文版)

基　　金：supported by National Natural Science Foundation of China(No.82372888);National Key Research and Development Program of China(No.2022YFC2704000);National Natural Science Foundation of China(No.82273383);the Capital’s Funds for Health Improvement and Research(No.2020-2-4098);Youth program of Beijing Municipal Natural Science Foundation(No.7204328);Clinical Medicine Plus X-Young Scholars Project,Peking University(No.PKU2022LCXQ020);Key Clinical Project of Peking University Third Hospital(No.BYSY2022050);Key Clinical Projects of Peking University Third Hospital(No.BYSYZD2021006);Key Clinical Projects of Peking University Third Hospital(No.BYSYZD2019034).

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.

关 键 词：High-grade serous ovarian cancer PD-1^(+)CD8^(+)T cells CD57^(+)CD8^(+)T cells PROGNOSIS biomarker 

分 类 号：R737.31[医药卫生—肿瘤]