BTN3A2 expression in epithelial ovarian cancer is associated with higher tumor infiltrating T cells and a better prognosis.

BTN3A2 expression in epithelial ovarian cancer is associated with higher tumor infiltrating T cells and a better prognosis.
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DOI:
10.1371/journal.pone.0038541
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Cailhier JF
Cailhier JF
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Le Page C;Marineau A;Bonza PK;Rahimi K;Cyr L;Labouba I;Madore J;Delvoye N;Mes-Masson AM;Provencher DM;Cailhier JF

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肿瘤细胞的BTN 3A 2/BT3.2亲丁酸蛋白mRNA表达先前被鉴定为高级别浆液性上皮性卵巢癌(HG-EOC)的小队列中的预后因子。在此,我们评估了199例HG-EOC患者标本中BT3.2蛋白水平的预后价值。由于亲丁酸蛋白的唯一已知作用是在免疫调节中,我们通过免疫组织化学用针对BT3.2、CD 3、CD 4、CD 8、CD 20、CD 68和CD 206的特异性抗体评估了BT3.2表达和免疫细胞的肿瘤内浸润之间的关联。上皮细胞BT3.2表达与较长的总生存期和较低的疾病进展风险显著相关(分别为HR = 0.651,p = 0.006和HR = 0.642,p = 0.002),并且与较高密度的浸润性T细胞,特别是CD 4+细胞显著相关(0.272,p<0.001)。        我们还观察到CD 206+细胞的相对密度(通过瘤内CD 206 +/CD 68+表达比率评估)与疾病进展风险之间存在强相关性(HR = 1.355 p = 0.044)。    总之,BT3.2蛋白是一个潜在的预后生物标志物,用于识别具有更好结局的HG-EOC患者。相反,高CD 206 +/CD 68+表达与疾病进展的高风险相关。虽然BT3.2的作用仍然未知,但我们的结果表明,上皮细胞表达BT3.2可能调节免疫细胞的肿瘤内浸润。
BTN3A2/BT3.2 butyrophilin mRNA expression by tumoral cells was previously identified as a prognostic factor in a small cohort of high grade serous epithelial ovarian cancer (HG-EOC). Here, we evaluated the prognostic value of BT3.2 at the protein level in specimen from 199 HG-EOC patients. As the only known role of butyrophilin proteins is in immune regulation, we evaluated the association between BT3.2 expression and intratumoral infiltration of immune cells by immunohistochemistry with specific antibodies against BT3.2, CD3, CD4, CD8, CD20, CD68 and CD206. Epithelial BT3.2 expression was significantly associated with longer overall survival and lower risk of disease progression (HR = 0.651, p = 0.006 and HR = 0.642, p = 0.002, respectively) and significantly associated with a higher density of infiltrating T cells, particularly CD4+ cells (0.272, p<0.001). We also observed a strong association between the relative density of CD206+ cells, as evaluated by the ratio of intratumoral CD206+/CD68+ expression, and risk of disease progression (HR = 1.355 p = 0.044, respectively). In conclusion, BT3.2 protein is a potential prognostic biomarker for the identification of HG-EOC patients with better outcome. In contrast, high CD206+/CD68+ expression is associated with high risk of disease progression. While the role of BT3.2 is still unknown, our result suggest that BT3.2 expression by epithelial cells may modulates the intratumoral infiltration of immune cells.
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