Unique Ectopic Lymph Node-Like Structures Present in Human Primary Colorectal Carcinoma Are Identified by Immune Gene Array Profiling
Unique Ectopic Lymph Node-Like Structures Present in Human Primary Colorectal Carcinoma Are Identified by Immune Gene Array Profiling
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DOI：
10.1016/j.ajpath.2011.03.007
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发表时间：
2011-07-01
影响因子：
6
通讯作者：
Mule, James J.
中科院分区：
文献类型：
--
作者：
Coppola, Domenico;Nebozhyn, Michael;Mule, James J.
我们假设免疫基因相关的特征可以预测结直肠癌（CRC）中淋巴细胞浸润的独特组织学特征，这些特征与临床参数相关。采用基因芯片技术对326例CRC进行了多基因分析，然后将其按低基因评分与高基因评分进行排序。显微镜下，具有高基因评分的CRC显示出明显的宿主免疫反应，明显地，组织为淋巴滤泡。增殖涉及B和T细胞。在每一个病例中，都发现了CD 79 a（+）B细胞前体的存在，这表明淋巴滤泡代表了新形成的异位淋巴结样结构。CD 21（+）树突状细胞存在于滤泡生发中心，CD 3（+）T细胞主要位于滤泡旁皮质区，围绕滤泡的B细胞区。12-趋化因子基因亚群的分子谱和异位淋巴结样结构的存在之间的强相关性与更好的患者生存相关，与肿瘤分期、部位位置、微卫星不稳定性或稳定性以及患者治疗无关。这些发现表明了有益的肿瘤内免疫细胞引发，并提高了基于分子特征的免疫治疗干预决策的可能性，这些分子特征可以识别肿瘤局部的异位淋巴结样结构的存在。(Am J Patbol 2011，179：37-45; DOI：10.1016/j.ajpath.2011.03.007）
We hypothesized that immune gene-related signatures would predict the presence of unique histological features of lymphoid cell infiltrates in colorectal carcinoma (CRC) that correlate with clinical parameters. Metagene.analysis with gene chip technology was performed on 326 CRCs, which were then sorted by low versus high gene scores. Microscopically, CRCs with a high gene score revealed a marked host immune response organized, remarkably, as lymphoid follicles. Proliferation involved both B and T cells. In every case, the presence of CD79a(+) B-cell precursors was identified, suggesting that the lymphoid follicles represent newly formed, ectopic lymph node-like structures. CD21(+) dendritic cells were present within the follicular germinal centers, and CD3(+) T cells were localized mainly in the para-follicular cortex zone surrounding the B-cell area of the follicles. A strong correlation between a 12-chemokine gene subset of the molecular profile and the presence of ectopic lymph node-like structures was associated with better patient survival independent of tumor staging, site location, microsatellite instability or stability, and patient treatment. These findings suggest beneficial, intratumoral immune cell priming and raise the possibility of immunotherapy intervention decisions based on molecular signatures that can identify the presence of tumor-localized, ectopic lymph node-like structures. (Am J Patbol 2011, 179:37-45; DOI: 10.1016/j.ajpath.2011.03.007)