Diversity Supplement Ifediora: Image-based models of tumor-immune dynamics in glioblastoma

多样性补充 Ifediora：胶质母细胞瘤肿瘤免疫动力学的基于图像的模型

• 批准号: 10746512
• 负责人: Peter Canoll
• 金额: $ 8.13万
• 依托单位: MAYO CLINIC ARIZONA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10746512
• 关键词: Advanced Malignant Neoplasm; Artificial Intelligence; Biology; Biopsy; Brain; Brain Neoplasms; Cell Communication; Cell Death Induction; Cells; Coculture Techniques; Computer Models; Disease; Early identification; Environment; Evolution; Genomics; Glioblastoma; Glioma; Image; Image Guided Biopsy; Immune; Immunologics; Immunotherapeutic agent; Immunotherapy; In Vitro; Interest Group; Link; Macrophage; Magnetic Resonance Imaging; Malignant Neoplasms; Maps; Methods; Microglia; Modeling; Myelogenous; Neuroglia; Patients; Pharmaceutical Preparations; Pharmacotherapy; Phenotype; Research; Signal Transduction; System; Therapeutic; Topotecan; Treatment Protocols; Tumor Promotion; aggressive therapy; anticancer research; biological heterogeneity; cancer care; cancer cell; cell type; chemotherapy; immunogenic cell death; immunoreactivity; individual patient; non-invasive imaging; parent grant; radiomics; response; single-cell RNA sequencing; tumor; tumor heterogeneity; tumor microenvironment

Abstract Glioblastoma Multiforme (GBM) is the most common of all gliomas with a median survival 14-18 months, despite aggressive treatment regimens. However, glioma is a disease that encompasses more than just cancer cells. In fact, many studies have shown that glioma can alter the brain microenvironment in ways that promote tumor survival and propagation. Within this brain tumor microenvironment is a diversity of cell types. One of particular group of interest is glioma associated microglia and macrophages (GAMMs), an important component of the immune cells in the brain. As a result, immunotherapy is emerging as a promising method to treat cancer; however, we are not able to identify early response or predict who will respond. While biopsies are the most reliable way to assess the immunological landscape within the tumor, we are limited both spatially and temporally in the number of biopsies we can obtain, particularly for brain tumor patients. The heterogeneity of the tumor-immune landscape across patients suggests that a patient-specific approach will be required to accurately assess each patient’s individual tumor-immune environment and the evolution thereof. As part of the Parent Grant, we will use non-invasive imaging, image-guided biopsies, computational modeling, and artificial intelligence to bridge spatial and temporal scales and predict the abundance of glioma associated microglia/macrophages (GAMMs) comprising each magnetic resonance image (MRI) at the voxel level. Linking the MRI to the biological heterogeneity using radiomics approaches provides an opportunity to individualize our understanding of the tumor-immune environment. Also in recent years, research has looked into how drug treatment is able to activate GAMMs to take on immunoreactive phenotypes. For this proposed supplement we will characterize myeloid – glioma cell interactions in response to immunogenic cell death induced by the chemotherapy drug topotecan. This will be done using MRI localized biopsies as well as in vitro co-culture systems, providing an additional therapeutically relevant context in which to study cellular response and signaling. The study will make use of single cell RNA sequencing to identify activational states of immune cells, and will provide us with another aspect of microglia and macrophage biology that can be incorporated into the model generated in the Parent Grant.

抽象的 胶质母细胞瘤多形（GBM）是所有神经胶质瘤中最常见的，中位生存率为14-18 月份，目的地积极的治疗方案。但是，神经胶质瘤是一种疾病 不仅包括癌细胞。实际上，许多研究表明神经胶质瘤可以 以促进肿瘤存活和传播的方式改变大脑微环境。之内 这种脑肿瘤微环境是细胞类型的多样性。特定兴趣群之一 是胶质瘤相关的小胶质细胞和巨噬细胞（GAMMS），这是该的重要组成部分 大脑中的免疫细胞。结果，免疫疗法正在成为一种有望的方法 治疗癌症；但是，我们无法确定早期的回应或预测谁将回应。 活检是评估免疫局势的最可靠的方式 肿瘤，我们在空间和临时都受到限制，在我们可以获得的活检数量中 特别是对于脑肿瘤患者。肿瘤免疫景观的异质性 患者建议需要采用特定患者的方法来准确评估每个方法 患者的单个肿瘤免疫环境及其进化。作为父母的一部分 格兰特，我们将使用非侵入性成像，图像引导的活检，计算建模和 人工智能桥接空间和临时尺度并预测神经胶质瘤的抽象 相关的小胶质细胞/巨噬细胞（GAMMS）完成每个磁共振图像 （MRI）在体素水平上。使用放射线学将MRI与生物制剂的异质性联系起来 方法提供了一个机会来个性化我们对肿瘤免疫的理解 环境。同样近年来，研究研究了药物治疗如何能够 激活伽玛以进行免疫反应性表型。对于拟议的补充，我们将 特征是髓样的 - 胶质瘤细胞相互作用，响应免疫原性死亡引起的 通过化学疗法药物拓扑丹。这将使用MRI局部活检以及 体外共培养系统，提供附加的治疗相关环境 研究细胞反应和信号传导。该研究将利用单细胞RNA测序 识别免疫细胞的活化状态，并将为我们提供小胶质细胞的另一个方面 可以纳入父授予赠款中产生的模型的巨噬细胞生物学。