Radiotherapy-induced tumor immunity

放射治疗诱导的肿瘤免疫

• 批准号: 9323354
• 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/9323354
• 关键词: Address; Affect; Aftercare; Androgens; Antibodies; Biological Assay; Biological Markers; Blood Platelets; CD4 Positive T Lymphocytes; CD8B1 gene; Cancer Patient; Cells; Clinical; Clinical Trials; Color; Communities; Cytotoxic T-Lymphocytes; Data; Development; Disease; Disease Progression; Dose; Dose Fractionation; Enzyme-Linked Immunosorbent Assay; Enzymes; Epitopes; Equilibrium; Erythrocytes; Exhibits; FOLH1 gene; Flow Cytometry; Fractionation; Frequencies; Helper-Inducer T-Lymphocyte; High-LET Radiation; Human; Immune; Immune response; Immune system; Immunologic Adjuvants; Immunologic Monitoring; Immunologics; 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 Cancer therapy; 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; Suppressor-Effector T-Lymphocytes; Systemic Therapy; T-Lymphocyte; Technology; Testing; Therapeutic; Thinking; Time; Tissues; Treatment Protocols; Tumor Antigens; Tumor Burden; Tumor Immunity; Variant; Work; base; cancer radiation therapy; cancer therapy; chemotherapy; deprivation; design; enzyme linked immunospot assay; immunological status; individual patient; innovation; monocyte; neutrophil; pre-clinical; prostatic fraction Acid phosphatase isoenzyme; public health relevance; response; response biomarker; 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（由申请人提供）：癌症放射治疗会产生系统性后果，这些后果是通过受照射组织和肿瘤中的危险信号介导的，并且会影响免疫系统。本提案旨在了解放射治疗中的不同剂量分割方案如何影响免疫系统。物理剂量递送的最新技术进步鼓励在更短的时间内创新地使用高于传统剂量/分次的剂量，但在人体中产生抗肿瘤而不是促肿瘤免疫反应的最佳剂量尚不清楚。临床前数据表明，8Gy 左右的剂量可能更好，这是通过免疫监测接受大分割治疗和常规治疗的前列腺癌患者所解决的问题。该研究以纵向方式设计，以检测个体患者在治疗前、治疗期间和治疗后随时间的变化。分析每个患者的免疫反应的多个方面，避免了个体差异的一些问题，这项研究的另一个好处来自于两个剂量分次方案将被并列比较。 -边在一个机构中，所采用的方法将基于尖端、复杂的免疫监测技术，以跟踪效应细胞和抑制性淋巴和骨髓来源的细胞以及体液反应的频率、表型和功能。 Dextramer 测定、ELISpot、多色流式细胞术、ELISA 和多重技术的目的是描绘包括肿瘤特异性反应（定性反应和多重反应）的整体免疫图景。 - 对于每个接受放射治疗的患者来说，它可能会为重新思考定量放射分割、危险信号的释放和肿瘤特异性免疫反应的发展提供数据。如果我们要将免疫系统纳入癌症治疗的背景下，特别是如果我们要将其与其他更系统的疗法（包括化疗）相结合，那么不同的放射剂量输送计划如何影响促肿瘤免疫反应和抗肿瘤免疫反应之间的平衡至关重要- (CT) 和免疫疗法 (IT)。作为快速转化应用程序，它还有可能产生巨大影响，因为它最终将使我们能够利用 通过创新方法发挥免疫系统的力量，将放射肿瘤学带入 21 世纪。