title: Systematic evaluation of multiple immune markers reveals prognostic factors in ovarian cancer.
abstract: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Several factors prognostic for survival have been identified including the presence of certain lymphocyte markers. Tumor-infiltrating lymphocytes (TILs), particularly cytotoxic CD8+ TILs, have been shown to be most favorable for prognosis in ovarian cancer, although other immune cells including CD3+ T-cells, CD4+ T-cells, and B-cells have also demonstrated survival benefits. Although data for these markers exists, results are not uniform in the literature. Furthermore, other immunomodulatory protein markers that have been targeted in effective immunotherapies for other malignancies may prove to be favorable in ovarian cancer.
  
  
  
  Here, extensive immunohistochemical analysis was performed on a tissue microarray, containing 135 ovarian cancer cases obtained during tumor debulking detecting 15 key lymphocyte markers such as CD3, CD4, and CD20, as well as activation and immunomodulatory molecules such as TIA-1 and PD-L1. Samples were analyzed for expression of markers in tumor islets or stroma and expression was correlated with overall survival, histotype, stage, age, debulking grade, and response to chemotherapy.
  
  
  
  Our results confirm the presence of CD8+ and CD20+ TILs is positively correlated with overall survival, with further multivariate modeling replicating that prognostic benefit. Additional markers of significant prognostic importance, including TIA-1, CD103 and HLA Class-II were also revealed.
  
  
  
  Our results further support the vital role of cytotoxic T-cells in defense against ovarian cancer and reveals new questions as to the role of B-cells in tumor control as well as the potential benefits of immunotherapy involving other immune modulating molecules.
authors.affiliation: Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Phillip P
authors.initials: PP
authors.lastname: Santoiemma
authors.affiliation: Department of Pathology & Laboratory Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Carolina
authors.initials: C
authors.lastname: Reyes
authors.affiliation: Department of Pathology & Laboratory Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Wang
authors.affiliation: Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Mike W
authors.initials: MW
authors.lastname: McLane
authors.affiliation: Department of Pathology & Laboratory Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Feldman
authors.affiliation: Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Janos L
authors.initials: JL
authors.lastname: Tanyi
authors.affiliation: Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology & Laboratory Medicine, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: poda@mail.med.upenn.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Powell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000401:mortality; D011379:Prognosis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D046888:Tissue Array Analysis
chemical_list: D015415:Biomarkers
keywords: Immunohistochemistry; Immunotherapy; Ovarian cancer; Tumor infiltrating lymphocytes; Tumor microarray