Prognostic and predictive role of spatially positioned tumour infiltrating lymphocytes in metastatic HER2 positive breast cancer treated with trastuzumab.
Prognostic and predictive role of spatially positioned tumour infiltrating lymphocytes in metastatic HER2 positive breast cancer treated with trastuzumab.
复制标题
DOI：
10.1038/s41598-017-18266-1
复制
发表时间：
2017-12-21
影响因子：
4.6
通讯作者：
Koivunen JP
中科院分区：
文献类型：
--
作者：
Honkanen TJ;Moilanen T;Karihtala P;Tiainen S;Auvinen P;Väyrynen JP;Mäkinen M;Koivunen JP
在曲妥珠单抗等靶向治疗进入临床实践后，HER2+乳腺癌的疾病结局发生了巨大变化，但曲妥珠单抗敏感性和耐药性的预测因素往往未知。目前的研究包括转移性乳腺癌患者(n = 48例)，他们接受曲妥珠单抗治疗，并有治疗前的肿瘤样本可用。对肿瘤进行T细胞(CD3、CD8)、自然杀伤(NK)细胞(CD56)和巨噬细胞(CD68)标记的免疫染色，并利用计算机图像分析系统对肿瘤不同部位的免疫细胞进行定量分析。高数量的CD3和CD8阳性T细胞与肿瘤中心(CT)的显著生存益处相关(p = 0.007，p = 0.001)，但在浸润性边缘无关。CT中NK细胞和巨噬细胞的数量对提高存活率的趋势不明显。在亚组分析中，CD8CT细胞的高密度与非骨性疾病、TX或T1-3以及ER+肿瘤的显著生存益处相关(p = 0.006，p = 0.003，p = 0.001)。此外，高CD8 CT细胞密度与曲妥珠单抗反应中断时间延长显著相关。这些结果提示，在转移性HER2+乳腺癌中，肿瘤中心的肿瘤浸润性淋巴细胞具有重要的预后和预测作用。
Disease outcomes of HER2+ breast cancers have dramatically changed after targeted therapies, such as trastuzumab, came to clinical practice but predictive factors for trastuzumab sensitivity and resistance are frequently unknown. Current work included metastatic breast cancer patients (n = 48), who were treated with trastuzumab and had pre-treatment tumour samples available. The tumours were immunostained for T-cell (CD3, CD8), natural killer (NK)-cell (CD56) and macrophage (CD68) markers and quantitative analysis of the immune cells was carried out using a computer-assisted image analysis in different tumour locations. High number of CD3 and CD8 positive T-cells was associated with significant survival benefit in the center of the tumour (CT) (p = 0.007, p = 0.001) but not in the invasive margin. The number of NK-cells and macrophages in the CT showed non-significant tendency towards improved survival. In subgroup analyses, high density of CD8 CT cells was associated with significant survival benefit in non-bone only disease, in TX or T1-3, and in ER+ tumours (p = 0.006, p = 0.003, p = 0.001). Moreover, high CD8 CT cell density associated significantly with long trastuzumab interruption periods in response. The results suggest important prognostic and predictive role of tumour infiltrating lymphocytes in center of the tumours in metastatic HER2+ breast cancer.
登录
查看更多内容
影响因子：
--
作者：
de Melo Gagliato D;Jardim DL;Marchesi MS;Hortobagyi GN
通讯作者：
Hortobagyi GN
影响因子：
11.5
作者：
Van der Auwera, I;Van Laere, SJ;Dirix, LY
通讯作者：
Dirix, LY
DOI：
10.1093/annonc/mdu385
发表时间：
2014-10
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Cardoso F;Costa A;Norton L;Senkus E;Aapro M;André F;Barrios CH;Bergh J;Biganzoli L;Blackwell KL;Cardoso MJ;Cufer T;El Saghir N;Fallowfield L;Fenech D;Francis P;Gelmon K;Giordano SH;Gligorov J;Goldhirsch A;Harbeck N;Houssami N;Hudis C;Kaufman B;Krop I;Kyriakides S;Lin UN;Mayer M;Merjaver SD;Nordström EB;Pagani O;Partridge A;Penault-Llorca F;Piccart MJ;Rugo H;Sledge G;Thomssen C;Van't Veer L;Vorobiof D;Vrieling C;West N;Xu B;Winer E
通讯作者：
Winer E
影响因子：
45.3
作者：
Mahmoud, Sahar M. A.;Paish, Emma Claire;Green, Andrew R.
通讯作者：
Green, Andrew R.
影响因子：
8.8
作者：
Vayrynen, J. P.;Tuomisto, A.;Makinen, M. J.
通讯作者：
Makinen, M. J.