title: Combined Immunoscore of CD103 and CD3 Identifies Long-Term Survivors in High-Grade Serous Ovarian Cancer.
abstract: OBJECTIVE
  Increased numbers of tumor-infiltrating lymphocytes (TILs) in high-grade serous ovarian cancer (HGSC) are associated with improved clinical outcome. Intraepithelial localization of TILs might be regulated by specific homing receptors, such as CD103, which is widely expressed by intraepithelial lymphocytes. Given the emerging role of CD103 TILs, we aimed to assess their contribution to the prognostic value of immunoscoring in HGSC.
  
  
  METHODS
  The density of intratumoral CD3 and CD103 lymphocytes was examined by immunohistochemistry on a tissue microarray of a series of 135 patients with advanced HGSC and correlated with CD4, CD8, CD56, FoxP3, and TCRγ T-cell counts, as well as E-cadherin staining and conventional prognostic parameters and clinical outcome.
  
  
  RESULTS
  Both the presence of CD103 cells, as well as high numbers of intraepithelial CD3 lymphocytes (CD3E), showed a significant correlation with overall survival, in the complete series, as well as in patients with optimal debulking and/or platinum sensitivity. Combining CD3 and CD103 counts improved prognostication and identified 3 major subgroups with respect to overall survival. The most pronounced effect was demonstrated for patients with optimally resected and platinum-sensitive tumors. Patients with CD3/CD103 tumors showed a 5-year survival rate at 90%, CD3/CD103 at 63%, and CD3/CD103 at 0% (P < 0.001).
  
  
  CONCLUSIONS
  These results suggest that combined assessment of CD103 and CD3 counts improves the prognostic value of TIL counts in HGSC and might identify patients with early relapse or long-term survival based on the type and extent of the immune response.
authors.affiliation: *Institute of Pathology, and †Department of Obstetrics and Gynecology, University Hospital of Tübingen; ‡Department of Immunology, Institute of Cell Biology, University of Tübingen; and §German Cancer Consortium (DKTK), DKFZ partner site Tübingen, Tübingen, Germany.
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Bösmüller
authors.forename: Philipp
authors.initials: P
authors.lastname: Wagner
authors.forename: Janet Kerstin
authors.initials: JK
authors.lastname: Peper
authors.forename: Heiko
authors.initials: H
authors.lastname: Schuster
authors.forename: Deborah Lam
authors.initials: DL
authors.lastname: Pham
authors.forename: Karen
authors.initials: K
authors.lastname: Greif
authors.forename: Christine
authors.initials: C
authors.lastname: Beschorner
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanović
authors.forename: Falko
authors.initials: F
authors.lastname: Fend
authors.forename: Annette
authors.initials: A
authors.lastname: Staebler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018284:Cystadenocarcinoma, Serous / Q000276:immunology / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D039001:Integrin alpha Chains / Q000378:metabolism*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D017741:Survivors; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D017252:CD3 Complex; D039001:Integrin alpha Chains; C091367:alpha E integrins