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

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/8549182
• 关键词: Binding; Biological Assay; Biological Markers; Cell physiology; Cells; Clinical Trials; Cytotoxic T-Lymphocyte-Associated Protein 4; Development; Early Diagnosis; FDA approved; Figs - dietary; Formalin; Functional RNA; Gene Expression; Human; Immune; Immunotherapeutic agent; Immunotherapy; Individual; Intervention; Malignant Neoplasms; Mediating; Metastatic Melanoma; MicroRNAs; Molecular Profiling; Neoplasm Metastasis; Outcome; Paraffin Embedding; Patients; Peripheral; Radiation therapy; Recombinants; Relative (related person); Reporting; Resistance; Serum; Side; T-Cell Activation; T-Lymphocyte; Testing; Therapeutic; Tissues; Transcript; Tumor Tissue; Unresectable; cancer type; chemotherapy; conventional therapy; design; human monoclonal antibodies; melanoma; neoplastic cell; outcome forecast; response; therapeutic target; therapy resistant; tumor

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（申请人提供）：恶性黑色素瘤（MM）是人类侵袭性最强的癌症之一，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治疗表现出持久的反应。因此，迫切需要个性化的策略来开发可以指导个体患者选择适当治疗的测定。发现免疫治疗反应的预测性生物标志物是实现这一目标的重要策略，这在本RFA的“挑衅性问题”中有所阐述。MicroRNA（miRNA）是一类调控基因表达的非编码小RNA。在多种类型的癌症中发现肿瘤细胞中改变的miRNA表达，并且有助于某些癌症的治疗抗性。我们最近发现miRNAs参与免疫细胞的发育和功能，MM患者的无细胞血清中含有MM特异性miRNAs，这些miRNAs可能作为MM早期诊断和预后的生物标志物。本申请旨在检验以下假设：在MM肿瘤或治疗靶向T细胞中，可以在对免疫疗法有反应和有抗性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，血清可以潜在地作为方便的、非侵入性的生物标志物，用于预测对免疫疗法的反应。我们将开始使用TaqMan TR-PCR阵列鉴定治疗反应性和治疗耐药患者之间的肿瘤特异性（Aim 1）和T细胞特异性（Aim 2）miRNA表达谱;然后定义血清特异性miRNA。这些开创性研究的结果可能使我们能够使用组织/血清miRNAs作为生物标志物来预测对免疫治疗有反应的MM患者，并且还可能促进新的干预策略的开发，以增加MM的免疫治疗。