title: Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer.
abstract: BACKGROUND
  Although tumor-infiltrating T cells have been documented in ovarian carcinoma, a clear association with clinical outcome has not been established.
  
  
  METHODS
  We performed immunohistochemical analysis of 186 frozen specimens from advanced-stage ovarian carcinomas to assess the distribution of tumor-infiltrating T cells and conducted outcome analyses. Molecular analyses were performed in some tumors by real-time polymerase chain reaction.
  
  
  RESULTS
  CD3+ tumor-infiltrating T cells were detected within tumor-cell islets (intratumoral T cells) in 102 of the 186 tumors (54.8 percent); they were undetectable in 72 tumors (38.7 percent); the remaining 12 tumors (6.5 percent) could not be evaluated. There were significant differences in the distributions of progression-free survival and overall survival according to the presence or absence of intratumoral T cells (P<0.001 for both comparisons). The five-year overall survival rate was 38.0 percent among patients whose tumors contained T cells and 4.5 percent among patients whose tumors contained no T cells in islets. Significant differences in the distributions of progression-free survival and overall survival according to the presence or absence of intratumoral T cells (P<0.001 for both comparisons) were also seen among 74 patients with a complete clinical response after debulking and platinum-based chemotherapy: the five-year overall survival rate was 73.9 percent among patients whose tumors contained T cells and 11.9 percent among patients whose tumors contained no T cells in islets. The presence of intratumoral T cells independently correlated with delayed recurrence or delayed death in multivariate analysis and was associated with increased expression of interferon-gamma, interleukin-2, and lymphocyte-attracting chemokines within the tumor. The absence of intratumoral T cells was associated with increased levels of vascular endothelial growth factor.
  
  
  CONCLUSIONS
  The presence of intratumoral T cells correlates with improved clinical outcome in advanced ovarian carcinoma.
authors.affiliation: Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Jose R
authors.initials: JR
authors.lastname: Conejo-Garcia
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Katsaros
authors.forename: Phyllis A
authors.initials: PA
authors.lastname: Gimotty
authors.forename: Marco
authors.initials: M
authors.lastname: Massobrio
authors.forename: Giorgia
authors.initials: G
authors.lastname: Regnani
authors.forename: Antonis
authors.initials: A
authors.lastname: Makrigiannakis
authors.forename: Heidi
authors.initials: H
authors.lastname: Gray
authors.forename: Katia
authors.initials: K
authors.lastname: Schlienger
authors.forename: Michael N
authors.initials: MN
authors.lastname: Liebman
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Rubin
authors.forename: George
authors.initials: G
authors.lastname: Coukos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000276:immunology; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D016133:Polymerase Chain Reaction; D016019:Survival Analysis; D013601:T-Lymphocytes