弗吉尼亚州立大学梅西癌症中心的研究人员已发现一个新生物标志物，这个新生物标志物与机体免疫系统相关，可预测乳腺癌病人复发风险。这个突破可能导致形成进一步个性化乳腺癌护理的新遗传测试。
这项研究发表在期刊《乳腺癌研究与治疗》（Breast Cancer Research and Treatment）上，它是第一个用定位于肿瘤上的肿瘤浸润免疫细胞来预测癌症复发的研究。用乳腺癌患者的组织样本，研究人员发现了与肿瘤浸润免疫细胞相关的特异五基因标签，它能精确地预测无复发存活。当前，有2个主要测试用于预测乳腺癌患者复发风险，即21基因检测（Oncotype DX panel）和70种基因表达谱检测（MammaPrint panel）。这两种检测都集中于肿瘤细胞主要表达的基因。
"我们知道，当机体检测到癌症时，便引发免疫反应，免疫系统细胞通常出现在肿瘤位置上。" 这项研究的主要研究人员、弗吉尼亚州立大学梅西癌症中心微生物学与免疫学副教授D.V.M.博士说，"我们的测试不同于当前使用的测试，它通过寻找针对癌症出现的生物学反应，而不依赖于因实际癌症细胞的基因表达。"
组织样本收集自乳腺癌女性患者，保存于美国梅西中心组织和数据采集分析核心（TDAAC）超过7年时间。Manjili 说，"我们研究了17个患者的数据，这些患者中，8个在5年内复发，9个保持无癌症至7年。"5基因标签预测这些病人复发的准确率大于85%。
Manjili和他的团队接下来将研究更大量患者的组织样本，以进一步证实该研究中的发现。他们还打算在治疗中乳腺癌病人的长期研究中测试他们的发现。
Manjili说："我们的发现能导致形成临床试验，以测试在高复发风险的乳腺癌患者中使用免疫疗法优先于常规治疗，这里的免疫疗法能起动患者免疫系统来阻止复发的可能，更象一个疫苗。”（生物谷bioon.com)
doi:10.1007/s10549-011-1470-x
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A signature of immune function genes associated with recurrence-free survival in breast cancer patients.
Ascierto ML, Kmieciak M, Idowu MO, Manjili R, Zhao Y, Grimes M, Dumur C, Wang E, Ramakrishnan V, Wang XY, Bear HD, Marincola FM, Manjili MH.
Abstract The clinical significance of tumor-infiltrating immune cells has been reported in a variety of human carcinomas including breast cancer. However, molecular signature of tumor-infiltrating immune cells and their prognostic value in breast cancer patients remain elusive. We hypothesized that a distinct network of immune function genes at the tumor site can predict a low risk versus high risk of distant relapse in breast cancer patients regardless of the status of ER, PR, or HER-2/neu in their tumors. We conducted retrospective studies in a diverse cohort of breast cancer patients with a 1-5 year tumor relapse versus those with up to 7 years relapse-free survival. The RNAs were extracted from the frozen tumor specimens at the time of diagnosis and subjected to microarray analysis and real-time RT-PCR. Paraffin-embedded tissues were also subjected to immunohistochemistry staining. We determined that a network of immune function genes involved in B cell development, interferon signaling associated with allograft rejection and autoimmune reaction, antigen presentation pathway, and cross talk between adaptive and innate immune responses were exclusively upregulated in patients with relapse-free survival. Among the 299 genes, five genes which included B cell response genes were found to predict with >85% accuracy relapse-free survival. Real-time RT-PCR confirmed the 5-gene prognostic signature that was distinct from an FDA-cleared 70-gene signature of MammaPrint panel and from the Oncotype DX recurrence score assay panel. These data suggest that neoadjuvant immunotherapy in patients with high risk of relapse may reduce tumor recurrence by inducing the immune function genes.
