Anatomic Pathology Division, Moffitt Cancer Center, Tampa, FL 33612-9497, USA.
Am J Pathol. 2011 Jul;179(1):37-45. doi: 10.1016/j.ajpath.2011.03.007. Epub 2011 May 3.
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 parafollicular 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.
我们假设免疫基因相关特征将预测结直肠癌（CRC）中独特的淋巴样细胞浸润的组织学特征的存在，这些特征与临床参数相关。对 326 例 CRC 进行了基因芯片技术的元基因分析，然后根据低基因评分与高基因评分进行排序。显微镜下，高基因评分的 CRC 显示出明显的宿主免疫反应，组织形式为淋巴滤泡。增殖涉及 B 细胞和 T 细胞。在每种情况下，均鉴定出 CD79a(+)B 细胞前体的存在，表明淋巴滤泡代表新形成的、异位淋巴结样结构。滤泡生发中心内存在 CD21(+)树突状细胞，CD3(+)T 细胞主要定位于滤泡 B 细胞区周围的滤泡旁皮质区。分子谱中 12 种趋化因子基因亚组的存在与异位淋巴结样结构的存在之间存在强烈相关性，与肿瘤分期、部位、微卫星不稳定性或稳定性以及患者治疗无关，与患者生存有关。这些发现提示有益的肿瘤内免疫细胞启动，并提出了基于可识别肿瘤定位的异位淋巴结样结构的分子特征进行免疫治疗干预决策的可能性。
