Zhang Jie, He Tianhui, Yin Zhongnan, Shang Chunliang, Xue Lixiang, Guo Hongyan
Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
Cancer Center, Peking University Third Hospital, Beijing, China.
Front Oncol. 2022 Jul 7;12:864021. doi: 10.3389/fonc.2022.864021. eCollection 2022.
Senescent T cells are reported to be increased in patients with cancer and are poor prognostic indicators. However, the distribution of senescent T cells and their correlation with clinical features in high-grade serous ovarian cancer (HGSOC) is unknown. We detected the percentage of senescent T cells in the peripheral blood and ascites of patients with advanced HGSOC (n = 86) at diagnosis by flow cytometry. Compared with healthy donors, patients with HGSOC exhibited an accumulation of CD28CD57 (Tsen) CD8 T cells in the peripheral blood and ascites. The frequency of Tsen CD8 T cells in the peripheral blood was positively correlated with age and pretreatment serum CA125 and increased in patients with large volume ascites, whereas the frequency of Tsen CD8 T cells in ascites was elevated in patients with lymph node metastasis. Patients with Tsen-high in ascites (>19.92%), but not in the peripheral blood, were more likely to be resistant to chemotherapy and had shorter progression-free survival. Tsen CD8 T cells exhibited common senescence features including increased SA-β-gal activity, declines in proliferation, loss of CD27 and gain of KLRG-1, and the production of cytokines. In ascites, the percentage of Tsen CD8 T cells was positively correlated with levels of interleukin-10 and granzyme B. This study suggests the potential of ascitic Tsen CD8 T cells at diagnosis as a prognostic biomarker in HGSOC.
据报道，癌症患者体内衰老T细胞增多，且是不良预后指标。然而，高级别浆液性卵巢癌（HGSOC）中衰老T细胞的分布及其与临床特征的相关性尚不清楚。我们通过流式细胞术检测了86例晚期HGSOC患者在诊断时外周血和腹水中衰老T细胞的百分比。与健康供体相比，HGSOC患者外周血和腹水中CD28-CD57（Tsen）CD8+ T细胞积聚。外周血中Tsen CD8+ T细胞频率与年龄和治疗前血清CA125呈正相关，且在大量腹水患者中升高，而腹水中Tsen CD8+ T细胞频率在有淋巴结转移的患者中升高。腹水中Tsen高（>19.92%）但外周血中不高的患者更可能对化疗耐药且无进展生存期较短。Tsen CD8+ T细胞表现出常见的衰老特征，包括β-半乳糖苷酶活性增加、增殖能力下降、CD27丢失和KLRG-1增加以及细胞因子产生。在腹水中，Tsen CD8+ T细胞百分比与白细胞介素-10和颗粒酶B水平呈正相关。本研究提示诊断时腹水中的Tsen CD8+ T细胞有可能作为HGSOC的预后生物标志物。
