PD-1⁺CD8⁺肿瘤浸润淋巴细胞和CD57⁺CD8⁺肿瘤腹水淋巴细胞的综合评分与晚期高级别浆液性卵巢癌患者的预后及肿瘤免疫微环境相关。

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.

作者信息

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

机构信息

Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.

Center of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China.

出版信息

Chin J Cancer Res. 2025 Jan 30;37(1):73-89. doi: 10.21147/j.issn.1000-9604.2025.01.06.

DOI:10.21147/j.issn.1000-9604.2025.01.06

PMID:40078557

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11893342/

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 CD57CD8 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 CD57CD8 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-1CD8 TILs (>87.8%) exhibited longer platinum-free interval (PFI) and overall survival (OS). In contrast, those with elevated CD57CD8 TALs (>28.69%) were more likely to experience chemotherapy and had lower complete remission rates, shorter PFI and OS. PD-1CD8 TILs are primarily displayed an effector memory state with strong proliferative and secretory capabilities. Approximately 50% of CD57CD8 TALs were terminally differentiated, exhibiting significantly impaired proliferation. Based on the proportions of PD-1CD8 TILs and CD57CD8 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-1CD8 TILs and higher CD57CD8 TALs, assessed prior to treatment, correlated with poor prognosis and suppressive TIME in advanced HGSOC.

摘要

目的

程序性死亡受体1（PD-1）在CD8⁺ T细胞上的表达与其激活和耗竭相关，而CD57作为衰老标志物。PD-1和CD57⁺CD8⁺ T细胞对晚期高级别浆液性卵巢癌（HGSOC）患者预后的影响尚不清楚。

方法

我们使用流式细胞术评估肿瘤浸润淋巴细胞（TILs，n = 85）和肿瘤腹水淋巴细胞（TALs，n = 87）中PD-1和CD57⁺CD8⁺ T细胞的百分比。通过对数秩最大化方法确定这些标志物在TILs和TALs中的最佳临界值。基因表达分析阐明了肿瘤免疫微环境（TIME，n = 36）。

结果

PD-1⁺CD8⁺ TILs水平较高（>87.8%）的患者无铂间期（PFI）和总生存期（OS）较长。相比之下，CD57⁺CD8⁺ TALs水平升高（>28.69%）的患者更易接受化疗，完全缓解率较低，PFI和OS较短。PD-1⁺CD8⁺ TILs主要表现为效应记忆状态，具有较强的增殖和分泌能力。约50%的CD57⁺CD8⁺ TALs处于终末分化状态，增殖能力明显受损。根据PD-1⁺CD8⁺ TILs和CD57⁺CD8⁺ TALs的比例，将患者分为预后良好、中等和不良组，PFI中位数分别为47.78、27.29和11.96个月（P<0.0001）。这些组的OS中位数分别为未达到、49.23和30.92个月（P<0.0001）。预后不良的患者在TIME中CD8⁺ T细胞比例显著降低，M2巨噬细胞增加，同时多个T细胞激活相关途径下调。