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

Abstract

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.

PD-1 + CD8 + TILs and CD57 + CD8 + TALs are associated with Prognosis of Patients with Advanced HGSOC

“…Our preliminary work found increased senescent CD8 + PBLs of advanced HGSOC patients compared with healthy volunteers, suggesting that T-cell senescence may be associated with cancer diagnosis. However, senescent CD8 + PBLs showed no correlation with progression free survival in advanced HGSOC [20].…”

“…Nevertheless, senescent CD8 + TALs were closely associated with cancer progression [20]. Therefore, it is of great value to analyze the dysfunctional status of T-cells in the tumors and ascites of HGSOC patients.…”

A Novel Score Using Lymphocyte-to-Monocyte Ratio in Blood and Malignant Body Fluid for Predicting Prognosis of Patients with Advanced Ovarian Cancer

“…Therefore, we are reporting this for the first time. Nevertheless, malignant body fluid in ovarian cancer is already showing promise both as a predictor of disease progression and as a substrate for monitoring drug response in immune target therapy [ 31 , 32 , 33 ]. Lane et al studied inflammation-regulating factors in ascites with advanced serous epithelial ovarian carcinoma [ 31 ] and found that IL-6 has a significant association with PFS in multivariate analysis.…”

“…Chen et al revealed that targeted cytokine (INF-gamma) expression level in ascites could serve as an immune biomarker for predicting outcomes in ovarian cancer [ 32 ]. Moreover, in a study by Zhang and colleagues, a high level of senescent T cells in ascites showed positive correlations with a short PFS and chemoresistance in advanced high grade serous ovarian cancer [ 33 ]. Of course, the generation of cell-mediated immune response depends on interactions of various cytokines.…”

UBE2T regulates epithelial–mesenchymal transition through the PI3K-AKT pathway and plays a carcinogenic role in ovarian cancer

“…Also, ovarian cancer affects the quality of life of patients. It is also related to many mechanisms, such as the angiogenic effects in ovarian cancer and mesothelial cells induced by Cu [ 6 ], high expression of Tsen CD8 T cells in ascites [ 7 ] and invasion of malignant ascites-derived EVs [ 8 ]. Hence, there is an urgent need to study the pathogenesis of this disease and discover sensitive and efficient markers for its effective diagnosis and treatment.…”