title: Intraepithelial T cells and tumor-associated macrophages in ovarian cancer patients.
abstract: The aims of this study were to evaluate the prognostic significance of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) in patients with familial ovarian cancer. Clinical and pathological information were retrieved from the Gilda Radner Familial Ovarian Cancer Registry (GRFOCR) in Buffalo, NY. Immunohistochemistry was performed on paraffin-embedded tissue specimens of GRFOCR participants using specific antibodies for CD3+, CD8+, CD25+, FOXP3+, CD68+, and CD163+. The correlation between the frequencies of TILs and TAMs and clinic-pathologic parameters were determined. Overall survival was determined using univariate and multivariate Cox proportional hazards models. High tumor grade correlated with higher frequencies of CD3+ (p = 0.019), CD68+ (p = 0.025), CD163+ (p = 0.018), and T(reg) (CD25+ FOXP3+) (p = 0.024) cells. Higher stage correlated with higher frequencies of CD163+ cells (p = 0.012). There were correlations between the frequencies of CD68+ and CD3+ (p = 0.029), between T(reg) and each of CD3+ (p = 0.002), CD8+ (p = 0.018), and CD68+ (p = 0.028) cells. In univariate analysis, age and T(reg) significantly predicted patient survival. In multivariate survival analysis, T(reg) frequency was the only significant predictor of prognosis in patients with familial ovarian cancer [HR = 0.92; 95% CI 0.87 - 0.98; p = 0.012]. We concluded that interaction between TILs and TAMs in familial EOC also exists, and tumors with high T(reg) frequencies have a more favorable outcome. Thus, therapeutic strategies to modulate tumor T(reg) infiltration could be beneficial for patients with familial ovarian cancer.
authors: Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. Paulette.mhawech-fauceglia@roswellpark.org
authors: Paulette
authors: P
authors: Mhawech-Fauceglia
authors: Dan
authors: D
authors: Wang
authors: Liaquat
authors: L
authors: Ali
authors: Shashikant
authors: S
authors: Lele
authors: Michael A
authors: MA
authors: Huba
authors: Song
authors: S
authors: Liu
authors: Kunle
authors: K
authors: Odunsi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004847:Epithelial Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008875:Middle Aged; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D013601:T-Lymphocytes / Q000276:immunology*
keywords: CD count; familial ovarian cancer; patient outcome
references: Gynecol Oncol. 2008 Feb;108(2):415-20
references: 18037158
references: Gynecol Oncol. 2008 May;109(2):215-9
references: 18314181
references: Cancer Immunol Immunother. 2004 Feb;53(2):64-72
references: 14593498
references: Obstet Gynecol. 1992 Oct;80(4):700-7
references: 1407898
references: CA Cancer J Clin. 2012 Jan-Feb;62(1):10-29
references: 22237781
references: Clin Cancer Res. 1998 Oct;4(10):2433-7
references: 9796975
references: Gynecol Oncol. 2010 May;117(2):366-72
references: 20144842
references: Eur J Gynaecol Oncol. 1996;17(3):169-76
references: 8780913
references: Eur J Surg Oncol. 2008 Feb;34(2):173-9
references: 17928188
references: J Clin Oncol. 2006 Feb 1;24(4):707-15
references: 16446345
references: Cancer. 2009 Jul 1;115(13):2891-902
references: 19472394
references: J Immunol. 2008 Oct 15;181(8):5396-404
references: 18832696
references: Br J Cancer. 2009 Nov 3;101(9):1513-21
references: 19861998
references: Gynecol Oncol. 2002 Apr;85(1):9-17
references: 11925114
references: Annu Rev Immunol. 2004;22:329-60
references: 15032581
references: Am J Hum Genet. 2001 Mar;68(3):700-10
references: 11179017
references: Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7875-80
references: 20385810
references: J Exp Med. 2006 Apr 17;203(4):871-81
references: 16606666
references: Am J Reprod Immunol. 2005 Dec;54(6):369-77
references: 16305662
references: N Engl J Med. 2003 Jan 16;348(3):203-13
references: 12529460
references: Int J Gynecol Cancer. 2007 Jul-Aug;17(4):764-70
references: 17309663
references: Cancer Res. 1995 Aug 1;55(15):3374-9
references: 7614474
references: Obstet Gynecol. 1984 Aug;64(2):195-9
references: 6738953
references: Cancer Res. 2007 Sep 15;67(18):8900-5
references: 17875732
references: Ann Intern Med. 2005 Sep 6;143(5):362-79
references: 16144895
references: Immunity. 2004 Aug;21(2):137-48
references: 15308095
references: Nat Med. 2004 Sep;10(9):942-9
references: 15322536
references: Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18538-43
references: 16344461
references: Am J Obstet Gynecol. 1988 Mar;158(3 Pt 1):678-9
references: 3348332
references: Int J Gynecol Pathol. 2000 Jan;19(1):7-15
references: 10638449
references: J Leukoc Biol. 2004 Jul;76(1):15-24
references: 14966194
references: Cancer Immunol Immunother. 2009 Mar;58(3):449-59
references: 18791714
references: PLoS One. 2009 Jul 29;4(7):e6412
references: 19641607
references: Gynecol Oncol. 2000 Aug;78(2):166-70
references: 10926797