microRNA as biomarkers for the response to immunotherapy in melanoma

microRNA 作为黑色素瘤免疫治疗反应的生物标志物

基本信息

批准号：
8549182
负责人：
QING-SHENG MI
金额：
$ 17.97万
依托单位：
HENRY FORD HEALTH SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-21 至 2015-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Malignant melanoma (MM) is one of the most invasive human cancers with its relative resistance to conventional chemotherapy and radiotherapy; only a small percentage of patients demonstrated durable responses to immunotherapy. Thus, a personalized strategy is urgently needed to develop assays which may guide the individual patient in the selection of appropriate therapy. Discovery of predictive biomarkers for immunotherapy response is an important strategy to attain this objective, which is stated in "Provocative Questions" for this RFA. MicroRNAs (miRNA) are small non-coding RNAs which regulate gene expression. Altered miRNA expression in tumor cells are found in variety types of cancer and contribute to therapy resistance in some cancer. We recently found that miRNAs are involved in immune cell development and function, and that cell-free serum from MM patients contains MM-specific miRNAs, which may serve as biomarkers for MM early diagnosis and prognosis. This application is designed to test the hypothesis that different miRNA expression profiles can be detected, either in MM tumor or in therapeutic targeting T cells, between patients who are responsive and who are resistant to immunotherapy. These differences could be reflected in the serum, which can potentially serve as convenient, noninvasive biomarkers for prediction of response to immunotherapy. We will begin by identifying the tumor-specific (Aim 1) and T cell-specific (Aim 2) miRNA expression profiles between therapy-responsive and therapy-resistant patients using TaqMan TR-PCR arrays; then will define serum specific miRNAs. The results from the proposed pioneering studies may enable us to predict MM patients who will respond to immunotherapy, using tissue/serum miRNAs as biomarkers, and may also facilitate the development of new intervention strategies for increasing immunotherapy for MM.

描述（由申请人提供）：恶性黑色素瘤（MM）是最具侵袭性的人类癌症之一，对常规化疗和放疗具有相对抵抗力；只有一小部分患者对免疫疗法表现出持久的反应。因此，迫切需要个性化策略来开发可以指导个体患者选择适当疗法的测定方法。发现免疫治疗反应的预测生物标志物是实现这一目标的重要策略，这一点在本次 RFA 的“挑衅性问题”中有所阐述。 MicroRNA (miRNA) 是调节基因表达的小非编码 RNA。在多种类型的癌症中都发现了肿瘤细胞中 miRNA 表达的改变，并导致某些癌症产生治疗耐药性。我们最近发现miRNA参与免疫细胞的发育和功能，并且MM患者的无细胞血清中含有MM特异性miRNA，这可能作为MM早期诊断和预后的生物标志物。该应用旨在测试以下假设：在 MM 肿瘤或治疗性靶向 T 细胞中，可以在对免疫疗法有反应和耐药的患者之间检测到不同的 miRNA 表达谱。这些差异可以反映在血清中，血清可以作为方便的、非侵入性的生物标志物来预测免疫治疗的反应。我们将首先使用 TaqMan TR-PCR 阵列识别治疗敏感患者和治疗抵抗患者之间的肿瘤特异性（目标 1）和 T 细胞特异性（目标 2）miRNA 表达谱；然后将定义血清特异性 miRNA。拟议的开创性研究的结果可能使我们能够使用组织/血清 miRNA 作为生物标志物来预测对免疫治疗有反应的 MM 患者，并且还可能有助于开发新的干预策略以增加 MM 的免疫治疗。