scholarly journals Higher Numbers of T-Bet+ Tumor-Infiltrating Lymphocytes Associate with Better Survival in Human Epithelial Ovarian Cancer

2017 ◽  
Vol 41 (2) ◽  
pp. 475-483 ◽  
Author(s):  
Yun Xu ◽  
Lujun Chen ◽  
Bin Xu ◽  
Yuqi Xiong ◽  
Min Yang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Flow Cytometry ◽  
Epithelial Ovarian Cancer ◽  
Cancer Patients ◽  
Tumor Infiltrating Lymphocytes ◽  
Lymphoid Cells ◽  
Type I ◽  
Flow Cytometry Analysis ◽  
Cancer Tissues ◽  
Infiltrating Lymphocytes

Background/Aims: T-bet, a member of the T-box family of transcription factors, is a key marker of type I immune response within the tumor microenvironment, and has been previously reported by us to serve as an important prognostic indicator for human gastric cancer patients and a potential biomarker for immunotherapy. In the present study, we aimed to assess the clinical significance and prognostic value of T-bet+ tumor-infiltrating lymphocytes in human epithelial ovarian cancer. Methods: The immunohistochemistry was used to analyze the infiltration density of T-bet+ lymphoid cells in human epithelial ovarian cancer tissues, and the flow cytometry analysis was used to further analyze the presence of T-bet+ tumor-infiltrating lymphocytes subgroups in cancer tissues. Results: Our immunohistochemistry analysis showed increased number of T-bet+ lymphoid cells in the human epithelial ovarian cancer tissues, and the flow cytometry analysis further demonstrated the presence of T-bet+ tumor-infiltrating lymphocytes subgroups including CD4+ , CD8+ T cells and NK cells. In addition, we also observed a significant association of T-bet+ tumor-infiltrating lymphocytes density in the tumor nest of cancer with not only serum CA125 levels but also with distant metastasis. However no association was observed with other characteristics like patients' age, pathological type, FIGO stage, tumor site and tumor size. Furthermore, the survival analysis showed that higher density of T-bet+ tumor-infiltrating lymphocytes both in tumor nest and tumor stroma of cancer tissues was significantly associated with better patient survival. In addition, the density of T-bet+ tumor-infiltrating lymphocytes in tumor nest appeared to be an independent risk factor for predicting patients’ postoperative prognoses. Conclusions: Our data indicated that the key transcription factor T-bet might play an important role in the type I immune cells mediated antitumor response, and the density of T-bet+ lymphocytes in human epithelial ovarian cancer tissues could serve as a prognostic predictor for ovarian cancer patients.

scholarly journals Assessment of the clinicopathological relevance of mesothelin level in plasma, peritoneal fluid, and tumor tissue of epithelial ovarian cancer patients

Tumor Biology ◽  
2018 ◽  
Vol 40 (10) ◽  
pp. 101042831880493 ◽  
Author(s):  
Karolina Okła ◽  
Justyna Surówka ◽  
Karolina Frąszczak ◽  
Arkadiusz Czerwonka ◽  
Katarzyna Kaławaj ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Patients ◽  
Peritoneal Fluid ◽  
Tumor Tissue ◽  
Benign Tumor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Type I ◽  
Primary Therapy ◽  
Tissue Levels

Ovarian cancer remains the most lethal gynecologic malignancy. This is due to lack of effective screening, diagnosis predominance in late stage of disease, a high recurrence rate after primary therapy, and poor treatment response in platinum-resistant tumor. Thus, unique biomarkers, predictive of individual disease course, and prognosis are urgently needed. The aim of our study was to assess the clinicopathological significance of plasma, peritoneal fluid, and tumor tissue levels of mesothelin in epithelial ovarian cancer patients. Plasma and peritoneal fluid levels of mesothelin were measured by enzyme-linked immunosorbent assay. Tissue expression of MSLN was evaluated using quantitative real-time polymerase chain reaction. Preoperative plasma mesothelin levels were significantly higher in epithelial ovarian cancer patients in comparison to the patients with benign tumor and controls. There have been noticed significant differences in the plasma mesothelin levels based on International Federation of Gynecology and Obstetrics stage, grade, and histology type. No significant changes were observed between Kurman and Shih type I versus type II epithelial ovarian cancer. Interestingly, peritoneal fluid mesothelin levels revealed significant differences based on both grade and Kurman and Shih–type epithelial ovarian cancer. There were no relevant changes in the mesothelin level in peritoneal fluid between different stages and histology types compared to benign tumor. MSLN expression level in tumor tissue was significantly higher based on stage, grade, and Kurman and Shih–type epithelial ovarian cancer than in the benign masses. In addition, data showed significant higher MSLN expression in endometrioid tumors compared to benign masses and serous tumors. Plasma, peritoneal fluid, and tumor tissue levels of mesothelin positively correlated with level of CA125. Low mesothelin concentrations in plasma were also associated with prolonged patient survival. More importantly, we revealed that plasma mesothelin level was correlated with both peritoneal fluid mesothelin level and tumor MSLN expression. This study highlights that plasma mesothelin level may be a useful noninvasive biomarker surrogate for local tumor mesothelin status in monitoring of epithelial ovarian cancer patients.

scholarly journals Clinical Significance of Tumor Infiltrating Lymphocytes in Association with Hormone Receptor Expression Patterns in Epithelial Ovarian Cancer

2021 ◽  
Vol 22 (11) ◽  
pp. 5714
Author(s):  
Gwan Hee Han ◽  
Ilseon Hwang ◽  
Hanbyoul Cho ◽  
Kris Ylaya ◽  
Jung-A Choi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Signaling Pathways ◽  
Hormone Receptor ◽  
Expression Patterns ◽  
Tumor Infiltrating Lymphocytes ◽  
Receptor Expression ◽  
Dominant Group ◽  
Hormone Receptor Expression ◽  
Infiltrating Lymphocytes

Hormone receptor expression patterns often correlate with infiltration of specific lymphocytes in tumors. Specifically, the presence of specific tumor-infiltrating lymphocytes (TILs) with particular hormone receptor expression is reportedly associated with breast cancer, however, this has not been revealed in epithelial ovarian cancer (EOC). Therefore, we investigated the association between hormone receptor expression and TILs in EOC. Here we found that ERα, AR, and GR expression increased in EOC, while PR was significantly reduced and ERβ expression showed a reduced trend compared to normal epithelium. Cluster analysis indicated poor disease-free survival (DFS) in AR+/GR+/PR+ subgroup (triple dominant group); while the Cox proportional-hazards model highlighted the triple dominant group as an independent prognostic factor for DFS. In addition, significant upregulation of FoxP3+ TILs, PD-1, and PD-L1 was observed in the triple dominant group compared to other groups. NanoString analyses further suggested that tumor necrosis factor (TNF) and/or NF-κB signaling pathways were activated with significant upregulation of RELA, MAP3K5, TNFAIP3, BCL2L1, RIPK1, TRAF2, PARP1, and AKT1 in the triple dominant EOC group. The triple dominant subgroup correlates with poor prognosis in EOC. Moreover, the TNF and/or NF-κB signaling pathways may be responsible for hormone-mediated inhibition of the immune microenvironment.

Sign in / Sign up

Export Citation Format

Share Document