Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer
Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer
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DOI：
10.1073/pnas.0509182102
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发表时间：
2005-12-20
影响因子：
11.1
通讯作者：
Odunsi, K
中科院分区：
文献类型：
--
作者：
Sato, E;Olson, SH;Odunsi, K
在最近的报道中，张等（2003）N。Engl.J。[文献348,203-213]，发现CD3（+）肿瘤浸润淋巴细胞（TILs）的存在与上皮性卵巢癌生存率的提高相关。我们对117例上皮性卵巢癌的TILs和癌睾丸抗原进行了免疫组化分析。研究了TILs亚群与睾丸癌抗原表达之间的关系，以及TILs与总生存率之间的关系。患者的中位随访时间为31个月。上皮内CD8(+) T细胞频率较高的患者与频率较低的患者相比，生存率更高[中位数= 55对26个月；风险比= 0.33；置信区间（ci）= 0.18 - -0.60;P = 0.0003]。CD3+ TILs或其他上皮内或间质TILs亚型未发现相关性。然而，上皮内CD8(+)/CD4(+) TIL比值高与低的亚组中位生存期分别为74个月和25个月（风险比= 0.30;ci = 0.16-0.55; P = 0.0001）。这些结果表明，CD4(+) TIL影响CD8+ TIL的有益作用。CD4+ T细胞对预后的不利影响是由于CD25（+）叉头盒P3 (FOXP3)（+）调节性T细胞（Treg；抑制性T细胞），CD8(+)/Treg比值高与低患者的生存率表明（中位数= 58 vs 23个月；风险比= 0.31；C.I. = 0.17-0.58; P = 0.0002）。上皮内CD8+ TILs的良好预后作用与NY-ESO-1或MAGE抗原的同时表达无关。我们得出结论，上皮内CD8+ TILs和高CD8+/Treg比值与上皮性卵巢癌的良好预后相关。
In a recent report, [Zhang etaL (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.