Cancer Immunity 2013; Vol. 13, p. 1

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 clinicpathologic 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 Treg (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 Treg and each of CD3+ (p = 0.002), CD8+ (p = 0.018), and CD68+ (p = 0.028) cells. In univariate analysis, age and Treg significantly predicted patient survival. In multivariate survival analysis, Treg 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 Treg frequencies have a more favorable outcome. Thus, therapeutic strategies to modulate tumor Treg infiltration could be beneficial for patients with familial ovarian cancer.