Dieu-Nosjean Marie-Caroline, Antoine Martine, Danel Claire, Heudes Didier, Wislez Marie, Poulot Virginie, Rabbe Nathalie, Laurans Ludivine, Tartour Eric, de Chaisemartin Luc, Lebecque Serge, Fridman Wolf-Herman, Cadranel Jacques
Laboratoire Microenvironnement, Immunitaire et Tumeurs, Institut National de la Santé et de la Recherche Médicale (INSERM) U872, Centre de Recherche des Cordeliers, Paris cedex 06, France.
J Clin Oncol. 2008 Sep 20;26(27):4410-7. doi: 10.1200/JCO.2007.15.0284.
It has been established that the immune system plays an important role in tumor rejection. There is also compelling evidence that immune responses can develop independently of secondary lymphoid organs in tertiary lymphoid structures. We studied the presence and the correlation of tertiary lymphoid structures with clinical outcome in non-small-cell lung cancer (NSCLC), as the prognostic value of these structures in patients with cancer had not yet been established.
This retrospective study was performed by immunohistochemistry on paraffin-embedded tissue specimens from 74 patients with early-stage NSCLC.
Tertiary lymphoid structures were detected in some tumors but not in nontumoral lungs. Thus we called these structures tumor-induced bronchus-associated lymphoid tissue (Ti-BALT). As in lymph nodes, Ti-BALTs were composed of mature dendritic cell (DC)/T-cell clusters adjacent to B-cell follicles and had features of an ongoing immune response. Because the quantitative counting of Ti-BALT was difficult to achieve, we used mature DCs that homed exclusively in Ti-BALT as a specific marker of these structures. Univariate analysis showed that the density of mature DCs was highly associated with a favorable clinical outcome (overall, disease-specific, and disease-free survival), suggesting that Ti-BALT may participate in antitumoral immunity. The density of tumor-infiltrating lymphocytes, in particular, CD4(+) and T-bet(+) Th1 T cells, was profoundly decreased in tumors weakly infiltrated by mature DCs.
The density of mature DCs was found to be a better predictor of clinical outcome than the other parameters tested. The number of tumor-infiltrating mature DCs may identify patients with early-stage NSCLC who have a high risk of relapse.
免疫系统在肿瘤排斥反应中发挥重要作用，这一点已得到证实。也有确凿证据表明免疫反应可在三级淋巴结构中独立于二级淋巴器官而发生。我们研究了三级淋巴结构在非小细胞肺癌（NSCLC）中的存在情况及其与临床结局的相关性，因为这些结构在癌症患者中的预后价值尚未确定。
本回顾性研究通过免疫组织化学方法对74例早期NSCLC患者石蜡包埋的组织标本进行检测。
在部分肿瘤中检测到三级淋巴结构，而在非肿瘤肺组织中未检测到。因此我们将这些结构称为肿瘤诱导的支气管相关淋巴组织（Ti - BALT）。与淋巴结一样，Ti - BALT由与B细胞滤泡相邻的成熟树突状细胞（DC）/T细胞簇组成，并具有正在进行的免疫反应特征。由于难以对Ti - BALT进行定量计数，我们使用仅归巢于Ti - BALT的成熟DC作为这些结构的特异性标志物。单因素分析显示成熟DC的密度与良好的临床结局（总生存期、疾病特异性生存期和无病生存期）高度相关，提示Ti - BALT可能参与抗肿瘤免疫。在成熟DC浸润较弱的肿瘤中，肿瘤浸润淋巴细胞尤其是CD4(+)和T - bet(+) Th1 T细胞的密度显著降低。
发现成熟DC的密度比所检测的其他参数更能预测临床结局。肿瘤浸润成熟DC的数量可能有助于识别有高复发风险的早期NSCLC患者。
