Immune Radiation Response Index (i- RRI) for Immune Cells from Normal and Tumor Microenvironments

项目摘要 “本申请是为了回应被标识为NOT-CA的特别利益通知（NOSI）而提交的- 21-083” 这项建议是为了回应上述最近公布的NCI特别利益通知， 行政补充资金，以支持免疫辐射反应指数（i-RRI）的发展。 罗格斯大学癌症研究所的新泽西是理想的适合这一补充资金与强大的司 放射肿瘤学系的放射肿瘤生物学项目和较强的免疫学 程序.我们的动物实验将利用我们开发的小鼠乳腺癌模型， 在研究中的广泛经验，重点是评估有效的抗肿瘤调节 免疫力除了具有进行拟议实验室研究和开发的全部能力外， iRRI是该研究提供的一种独特能力，它与目前正在进行的术前辐射相结合 已经招募了第一批患者的乳腺癌增强试验。我们将要研究的小鼠乳房模型 与这项人体试验相一致，使我们能够将小鼠模型的免疫生物标志物 在人类乳腺癌患者中进行术前放射增强后使用免疫生物标志物的实验。的 具体目标1：使用小鼠乳腺癌模型 在我们小组开发的允许体内免疫分析评价，我们将进行广泛的 在几种常用的辐射分级方案后进行免疫分析，以评估每种方案 分级方案影响免疫辐射反应指数的发展。具体目标二： 确定从对照小鼠和荷瘤小鼠中提取并扩增的免疫细胞是否在体外复制， 在我们的模型中体内观察到的辐射诱导的免疫应答的预测。具体目标3：评估 一项正在进行的术前放射增强人类乳腺癌试验， 在特定目标1的小鼠模型实验中评估的生物标志物与人乳腺相关 癌症体内手术前辐射。拟议的实验研究正在乳腺癌中进行 我们拥有放射生物学、临床和免疫生物标志物专业知识的细胞系和模型， 体验.我们的期望是，从基本实验中得到的信息将有助于 免疫辐射反应指数的定义和验证，这将反过来通知临床术前 关于术前放射的最佳分割方案的boost方案。

PROJECT ABSTRACT “This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 21-083.” This proposal is in response to the above recently announced Notice of Special Interest of the NCI for administrative supplemental funding to support development of an Immune Radiation Response Index (i-RRI). The Rutgers Cancer Institute of New Jersey is ideally suited for this supplemental funding with a strong Division of Radiation Cancer Biology program in the Department of Radiation Oncology and a strong immunology program. Our animal experiments will utilize a mouse breast cancer model that we have developed and have extensive experience in working with in studies focused on evaluating the regulation of effective antitumor immunity. In addition to having the full capabilities of conducting the proposed laboratory studies and develop the iRRI, a unique capability that the study provides is integration with a currently ongoing pre-operative radiation boost trial in breast cancer that has already enrolled its first patients. The mouse breast model we will be working with aligns with this human trial, allowing us to correlate the immune biomarkers from the mouse model experiments with immune biomarkers after a pre-operative radiation boost in human breast cancer patients. The specific aims of the current proposal are as follows: Specific Aim 1: Using a mouse breast cancer model developed in our group which allows for the evaluation of in-vivo immune analyses, we will conduct extensive immune analyses after several commonly employed radiation fractionation schemes to assess how each fractionation scheme influences the development of an immune radiation response index. Specific Aim 2: Determine if immune cells taken from control and tumor-bearing mice and expanded in-vitro replicates and allows the prediction of the radiation induced immune response seen in-vivo in our model. Specific Aim 3: Evaluate in an ongoing pre-operative radiation boost human breast cancer trial if the radiation induced immune response biomarkers assessed in the mouse model experiments from Specific Aim 1 correlate with the human breast cancer in-vivo pre-operative radiation. The proposed experimental studies are being performed in breast cancer cell lines and models where we have the radiation biology, clinical and immune biomarker expertise, and experience. Our expectation is that the information derived from the basic experiments will contribute to the definition and validation of an immune radiation response index that will in turn inform the clinical pre-operative boost protocol regarding the optimal fractionation scheme for pre-operative radiation.