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（由应用提供）：癌症的放射治疗具有系统性后果，这些后果是通过辐照组织和肿瘤中的危险信号传导介导的，并且可以吸引免疫系统。该建议旨在了解放射治疗中不同剂量分级时间表如何塑造免疫系统。物理剂量交付的最新技术进步鼓励了更短的时间内的创新使用高于传统剂量/分数。尚不清楚与人类中的亲肿瘤免疫调查相比，每分级分数的最佳剂量，但临床前数据表明，剂量约为8GY的剂量可能是优越的。这是免疫监测前列腺癌患者接受次序和常规方案的问题。该研究以纵向方式设计，可在治疗前，期间和之后随着时间的推移，证明其免疫调查的多个方面的变化。每位患者的时间构成免疫调查会汇总一些个体变异的问题。这项研究的另一个好处是，这两个剂量分级时间表将在一个机构中并排比较，这将使潜在的偏见最小化。所采用的方法将基于最先进的，先进的免疫监测技术，以跟踪效应子和抑制淋巴样和髓样衍生的细胞的频率，表型和功能以及体液反应。它们包括葡萄膜分析，ELISPOT，多色流式细胞仪，ELISA和多重技术。目的是画出包括肿瘤特异性反应的全球免疫力图片 - 定性以及 定量 - 对于每个患者接受放射治疗时。该研究将产生很大的影响。它可以为重新思考辐射分离，危险信号的释放以及肿瘤特异性免疫调查的新范式提供新的范式数据。如果我们要在癌症治疗的背景下参与免疫系统，尤其是如果我们要将其与其他更全面的治疗方法相结合，包括化学疗法（CT）和免疫疗法（IT），那么知道不同的辐射剂量递送时间表如何影响支持和抗肿瘤免疫调查的平衡至关重要。这项研究还有可能作为快速翻译应用产生巨大影响，因为它最终将使我们能够利用 免疫系统的力量采用创新方法，将辐射肿瘤学带到21世纪。