title: Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer.
abstract: In a recent report, [Zhang et al. (2003) N. Engl. J. Med. 348, 203-213], the presence of CD3+ tumor-infiltrating lymphocytes (TILs) was found to correlate with improved survival in epithelial ovarian cancer. We performed immunohistochemical analysis for TILs and cancer testis antigens in 117 cases of epithelial ovarian cancer. The interrelationship between subpopulations of TILs and expression of cancer testis antigens was investigated, as well as between TILs and overall survival. The median follow-up of the patients was 31 months. Patients with higher frequencies of intraepithelial CD8+ T cells demonstrated improved survival compared with patients with lower frequencies [median = 55 versus 26 months; hazard ratio = 0.33; confidence interval (C.I.) = 0.18-0.60; P = 0.0003]. No association was found for CD3+ TILs or other subtypes of intraepithelial or stromal TILs. However, the subgroups with high versus low intraepithelial CD8+/CD4+ TIL ratios had median survival of 74 and 25 months, respectively (hazard ratio = 0.30; C.I. = 0.16-0.55; P = 0.0001). These results indicate that CD4+ TILs influence the beneficial effects of CD8+ TIL. This unfavorable effect of CD4+ T cells on prognosis was found to be due to CD25+ forkhead box P3 (FOXP3)+ regulatory T cells (Treg; suppressor T cells), as indicated by survival of patients with high versus low CD8+/Treg ratios (median = 58 versus 23 months; hazard ratio = 0.31; C.I. = 0.17-0.58; P = 0.0002). The favorable prognostic effect of intraepithelial CD8+ TILs did not correlate with concurrent expression of NY-ESO-1 or MAGE antigens. We conclude that intraepithelial CD8+ TILs and a high CD8+/Treg ratio are associated with favorable prognosis in epithelial ovarian cancer.
authors.affiliation: Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Sato
authors.forename: Sara H
authors.initials: SH
authors.lastname: Olson
authors.forename: Jiyoung
authors.initials: J
authors.lastname: Ahn
authors.forename: Brian
authors.initials: B
authors.lastname: Bundy
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Denise
authors.initials: D
authors.lastname: Frosina
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Christine
authors.initials: C
authors.lastname: Ambrosone
authors.forename: James
authors.initials: J
authors.lastname: Kepner
authors.forename: Tosin
authors.initials: T
authors.lastname: Odunsi
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Shashikant
authors.initials: S
authors.lastname: Lele
authors.forename: Yao-Tseng
authors.initials: YT
authors.lastname: Chen
authors.forename: Haruo
authors.initials: H
authors.lastname: Ohtani
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016516:CD4-CD8 Ratio; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000276:immunology* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*