Radiotherapy-induced tumor immunity

放射治疗诱导的肿瘤免疫

• 批准号: 8963306
• 负责人: Dorthe Schaue
• 金额: $ 35.23万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8963306
• 关键词: Address; Affect; Aftercare; Androgens; Antibodies; Biological Markers; Blood Platelets; CD4 Positive T Lymphocytes; CD8B1 gene; Cancer Patient; Cells; Clinical; Clinical Trials; Color; Communities; Cytotoxic T-Lymphocytes; Data; Development; Diagnostic Neoplasm Staging; Disease; Disease Progression; Dose; Dose Fractionation; Enzyme-Linked Immunosorbent Assay; Enzymes; Epitopes; Equilibrium; Erythrocytes; Exhibits; Flow Cytometry; Fractionation; Frequencies; Glutamate Carboxypeptidase II; Helper-Inducer T-Lymphocyte; Human; Immune; Immune response; Immune system; Immunologic Adjuvants; Immunologic Monitoring; Immunosuppression; Immunotherapy; Impact evaluation; Individual; Inflammatory; Institution; Irradiated tumor; Leukocytes; Link; Longitudinal Studies; Lymphoid; Malignant Neoplasms; Malignant neoplasm of prostate; Measures; Mediating; Methods; Monitor; Myelogenous; Natural Killer Cells; Outcome; Paint; Patient Selection; Patients; Peptides; Phenotype; Prostate-Specific Antigen; Prostatic Neoplasms; Radiation; Radiation Oncology; Radiation therapy; Reactive Oxygen Species; Regimen; Regulatory T-Lymphocyte; Sampling; Schedule; Selection for Treatments; Serum Markers; Shapes; Side; Signal Transduction; Staging; Suppressor-Effector T-Lymphocytes; Systemic Therapy; T-Lymphocyte; Technology; Testing; Therapeutic; Thinking; Time; Treatment Protocols; Tumor Antigens; Tumor Burden; Tumor Immunity; Tumor Tissue; Variant; Work; base; cancer radiation therapy; cancer therapy; chemotherapy; deprivation; design; enzyme linked immunospot assay; innovation; monocyte; neutrophil; pre-clinical; prostatic fraction Acid phosphatase isoenzyme; public health relevance; response; success; survivin; translational study; treatment planning; tumor

 DESCRIPTION (provided by applicant): Radiation therapy for cancer has systemic consequences that are mediated through danger signaling in irradiated tissues and tumors and that engage the immune system. This proposal aims to understand how different dose-fractionation schedules in radiation therapy shape the immune system. Recent technological advances in physical dose delivery have encouraged innovative use of higher than conventional doses/fraction given over a shorter time. The optimal dose per fraction that generates anti-tumor as opposed to pro-tumor immune responses in humans is not known but preclinical data suggest that doses around 8Gy may be superior. This is the question addressed here by immune monitoring prostate cancer patients receiving hypofractionated and conventional regimens. The study is designed in a longitudinal fashion to detect changes in individual patients over time before, during and after treatment and to probe multiple aspects of their immune responses. Composing immune profiles with time for each patient circumvents some of the problems of individual variation. An additional benefit of this study comes from the fact that both dose-fractionation schedules will be compared side-by-side in one institution, which minimizes potential biases. The methods employed will be based on cutting-edge, sophisticated immune monitoring technologies to track the frequency, phenotype, and function of effector and suppressor lymphoid and myeloid-derived cells as well as humoral responses. They include Dextramer assay, ELISpot, multi-color flow cytometry, ELISA and multiplex technology. The aim is to paint a global immune picture that includes tumor-specific responses - qualitative as well as quantitative - for each patient as they undergo radiation treatment. The study will have high impact. It may provide data for a new paradigm for re-thinking radiation fractionation, the release of danger signals, and the development of tumor-specific immune responses. Knowing how different radiation dose delivery schedules affect the balance between pro- and anti-tumor immune responses is crucial if we are to engage the immune system in the context of cancer treatment, especially if we are to integrate it with other more systemic therapies, including chemo- (CT) and immunotherapy (IT). This study also has the potential to have an enormous impact as a fast-track translational application because it will ultimately allow us to harness the power of the immune system with an innovative approach that takes radiation oncology to the 21st century.

 描述(申请人提供)：癌症的放射治疗具有全身性后果，通过照射的组织和肿瘤中的危险信号来调节，并参与免疫系统。这项建议旨在了解放射治疗中不同的剂量分级计划如何塑造免疫系统。最近在物理剂量传递方面的技术进步鼓励创新地使用比在较短时间内给予的常规剂量/分数更高的剂量/分数。在人类中，产生抗肿瘤免疫反应而不是亲肿瘤免疫反应的每一部分的最佳剂量尚不清楚，但临床前数据表明，8GY左右的剂量可能更好。这就是接受低分割和常规方案的前列腺癌患者免疫监测所要解决的问题。这项研究是以纵向方式设计的，目的是检测个别患者在治疗前、治疗中和治疗后一段时间内的变化，并探索他们免疫反应的多个方面。根据每个患者的时间组成免疫配置文件，可以避开一些个体差异的问题。这项研究的另一个好处来自这样一个事实，即两种剂量分级计划将在一家机构中并排进行比较，从而将潜在的偏差降至最低。所采用的方法将基于尖端、复杂的免疫监测技术，以跟踪效应者和抑制者淋巴和髓系细胞的频率、表型和功能以及体液反应。这些方法包括DExtramer法、ELISpot法、多色流式细胞术、ELISA法和多重技术。其目的是描绘一幅全球免疫图景，其中包括肿瘤特异性反应-定性和 定量--每个患者在接受放射治疗时。这项研究将产生很大的影响。它可能为重新思考辐射分割、危险信号的释放和肿瘤特异性免疫反应的发展提供新的范例。如果我们要在癌症治疗中利用免疫系统，特别是如果我们要将其与其他更系统的治疗方法相结合，包括化疗(CT)和免疫治疗(IT)，了解不同的辐射剂量传递计划如何影响促肿瘤和抗肿瘤免疫反应之间的平衡是至关重要的。这项研究还有可能对快速通道翻译应用程序产生巨大影响，因为它最终将使我们能够利用 以一种创新的方法将放射肿瘤学带入21世纪，以增强免疫系统的力量。