Differential intratumoral distributions of CD8 and CD163 immune cells as prognostic biomarkers in breast cancer.
Differential intratumoral distributions of CD8 and CD163 immune cells as prognostic biomarkers in breast cancer.
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DOI：
10.1186/s40425-017-0240-7
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发表时间：
2017
影响因子：
10.9
通讯作者：
Baxevanis CN
中科院分区：
文献类型：
--
作者：
Fortis SP;Sofopoulos M;Sotiriadou NN;Haritos C;Vaxevanis CK;Anastasopoulou EA;Janssen N;Arnogiannaki N;Ardavanis A;Pawelec G;Perez SA;Baxevanis CN
肿瘤免疫细胞浸润在阻碍癌症进展中是必不可少的，并且可以补充TNM分类。CD 8+和CD 163+细胞在乳腺癌中具有预后影响，但其空间异质性在这种类型的癌症中尚未得到广泛研究。在此，根据其在肿瘤中心（TC）和肿瘤浸润边缘（IM）的组合密度，评估其作为预后生物标志物的潜力。通过福尔马林固定、石蜡包埋（FFPE）肿瘤组织样本的免疫组化定量CD 8+和CD 163+细胞，该样本来自一个队列，共162例患者，在2000年至2015年期间诊断为经组织学证实的原发性浸润性非转移性导管乳腺癌。其中97例患者获得了临床随访（中位6.9年）。TC和IM组合隔室中CD 8+和CD 163+细胞的差异密度（即，高（H）/低（L），分别用于CD 8+细胞，而反向L/H组合用于CD 163+细胞）被发现对生存具有显著的预后价值，并且允许比TNM分期、肿瘤大小、淋巴结浸润和组织学分级更好的患者分层。TC和IM中CD 8+和CD 163+细胞密度的联合评估进一步改善了基于无病生存期和总生存期的临床结局预测。尽管临床病理参数较差，但具有有利免疫特征的患者具有有利的临床结局。鉴于CD 8+和CD 163+细胞在调节相反的免疫回路中的重要作用，将其差异密度的评估添加到乳腺癌的预后生物标志物设备中将是有价值的。需要更大规模的验证研究来证实这些发现。研究代码：IRB-ID 6079/448/10-6-13批准日期：2013年10月6日回顾性研究（2000-2010）首例患者前瞻性入组2014年14月2日本文的在线版本（doi：10. 1186/s40425-017-0240-7）包含补充材料，可供授权用户使用。
Tumor immune cell infiltrates are essential in hindering cancer progression and may complement the TNM classification. CD8+ and CD163+ cells have prognostic impact in breast cancer but their spatial heterogeneity has not been extensively explored in this type of cancer. Here, their potential as prognostic biomarkers was evaluated, depending on their combined densities in the tumor center (TC) and the tumor invasive margin (IM). CD8+ and CD163+ cells were quantified by immunohistochemistry of formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples from a cohort totaling 162 patients with histologically-confirmed primary invasive non-metastatic ductal breast cancer diagnosed between 2000 and 2015. Clinical follow-up (median 6.9 years) was available for 97 of these patients. Differential densities of CD8+ and CD163+ cells in the combined TC and IM compartments (i.e., high(H)/low(L), respectively for CD8+ cells and the reverse L/H combination for CD163+ cells) were found to have significant prognostic value for survival, and allowed better patient stratification than TNM stage, tumor size, lymph node invasion and histological grade. The combined evaluation of CD8+ and CD163+ cell densities jointly in TC and IM further improves prediction of clinical outcomes based on disease-free and overall survival. Patients having the favorable immune signatures had favorable clinical outcomes despite poor clinicopathological parameters. Given the important roles of CD8+ and CD163+ cells in regulating opposing immune circuits, adding an assessment of their differential densities to the prognostic biomarker armamentarium in breast cancer would be valuable. Larger validation studies are necessary to confirm these findings. Study code: IRB-ID 6079/448/10-6-13 Date of approval: 10/06/2013 Retrospective study (2000–2010) First patient prospectively enrolled 14/2/2014 The online version of this article (doi:10.1186/s40425-017-0240-7) contains supplementary material, which is available to authorized users.