title: Higher Numbers of T-Bet+ Tumor-Infiltrating Lymphocytes Associate with Better Survival in Human Epithelial Ovarian Cancer.
abstract: OBJECTIVE
  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.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xu
authors.forename: Lujun
authors.initials: L
authors.lastname: Chen
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Xiong
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Rui
authors.forename: Liangrong
authors.initials: L
authors.lastname: Shi
authors.forename: Changping
authors.initials: C
authors.lastname: Wu
authors.forename: Jingting
authors.initials: J
authors.lastname: Jiang
authors.forename: Binfeng
authors.initials: B
authors.lastname: Lu
mesh_terms: D000368:Aged; D018394:CA-125 Antigen / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology; D009362:Neoplasm Metastasis; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis; D020825:T-Box Domain Proteins / Q000378:metabolism*; D000098815:T-bet Transcription Factor
chemical_list: D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor
keywords: Epithelial ovarian cancer; T-bet+; Tumor-infiltrating lymphocytes