Ascitic Senescent T Cells Are Linked to Chemoresistance in Patients With Advanced High-Grade Serous Ovarian Cancer

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 cel...

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Main Authors: Jie Zhang, Tianhui He, Zhongnan Yin, Chunliang Shang, Lixiang Xue, Hongyan Guo
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.864021/full
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author Jie Zhang
Jie Zhang
Jie Zhang
Tianhui He
Zhongnan Yin
Zhongnan Yin
Chunliang Shang
Lixiang Xue
Lixiang Xue
Hongyan Guo
author_facet Jie Zhang
Jie Zhang
Jie Zhang
Tianhui He
Zhongnan Yin
Zhongnan Yin
Chunliang Shang
Lixiang Xue
Lixiang Xue
Hongyan Guo
author_sort Jie Zhang
collection DOAJ
description 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 CD28−CD57+ (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.
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spelling doaj.art-1362e5504d88437b80a063c7593f40b42022-12-22T02:44:19ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-07-011210.3389/fonc.2022.864021864021Ascitic Senescent T Cells Are Linked to Chemoresistance in Patients With Advanced High-Grade Serous Ovarian CancerJie Zhang0Jie Zhang1Jie Zhang2Tianhui He3Zhongnan Yin4Zhongnan Yin5Chunliang Shang6Lixiang Xue7Lixiang Xue8Hongyan Guo9Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, ChinaCancer Center, Peking University Third Hospital, Beijing, ChinaCenter of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, ChinaDepartment of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, ChinaCancer Center, Peking University Third Hospital, Beijing, ChinaCenter of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, ChinaDepartment of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, ChinaCancer Center, Peking University Third Hospital, Beijing, ChinaCenter of Basic Medical Research, Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, ChinaDepartment of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, ChinaSenescent 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 CD28−CD57+ (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.https://www.frontiersin.org/articles/10.3389/fonc.2022.864021/fullsenescent T cellsHGSOCasciteschemosensitivitybiomarkers
spellingShingle Jie Zhang
Jie Zhang
Jie Zhang
Tianhui He
Zhongnan Yin
Zhongnan Yin
Chunliang Shang
Lixiang Xue
Lixiang Xue
Hongyan Guo
Ascitic Senescent T Cells Are Linked to Chemoresistance in Patients With Advanced High-Grade Serous Ovarian Cancer
Frontiers in Oncology
senescent T cells
HGSOC
ascites
chemosensitivity
biomarkers
title Ascitic Senescent T Cells Are Linked to Chemoresistance in Patients With Advanced High-Grade Serous Ovarian Cancer
title_full Ascitic Senescent T Cells Are Linked to Chemoresistance in Patients With Advanced High-Grade Serous Ovarian Cancer
title_fullStr Ascitic Senescent T Cells Are Linked to Chemoresistance in Patients With Advanced High-Grade Serous Ovarian Cancer
title_full_unstemmed Ascitic Senescent T Cells Are Linked to Chemoresistance in Patients With Advanced High-Grade Serous Ovarian Cancer
title_short Ascitic Senescent T Cells Are Linked to Chemoresistance in Patients With Advanced High-Grade Serous Ovarian Cancer
title_sort ascitic senescent t cells are linked to chemoresistance in patients with advanced high grade serous ovarian cancer
topic senescent T cells
HGSOC
ascites
chemosensitivity
biomarkers
url https://www.frontiersin.org/articles/10.3389/fonc.2022.864021/full
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