Cancer Center Support Grant

癌症中心支持补助金

基本信息

批准号：
10292997
负责人：
MICHAEL A TEITELL
金额：
$ 25万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-12-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10292997
关键词：
Address Applications Grants Area Biomedical Engineering Breast Cancer survivor Cancer Burden Cancer Center Support Grant Cancer Control Cancer Patient Cancer Survivorship Caring Catchment Area Cell Therapy Cells Clinical Clinical Research Clinical Sciences Clonal Evolution Colorectal Cancer Communication Communities Community Health Education Community Outreach Complement Comprehensive Cancer Center County Detection Diagnostic Early Diagnosis Education Educational workshop Electronic cigarette Environment Epigenetic Process Event Evolution FDA approved Faculty Fellowship Program Fostering Gene Expression Regulation Generations Genetic Grant Guidelines Healthcare Immigrant Immune Immune response Immune system Immunotherapy Individual Institution Intervention Studies Laboratories Leadership Learning Lesion Los Angeles Low income Malignant Neoplasms Malignant neoplasm of cervix uteri Malignant neoplasm of liver Malignant neoplasm of lung Mentors Metabolic Minority Groups Mission Nanotechnology Neoplasm Metastasis Obesity Occupations Organizational Change Patient Care Patients Population Sciences Postdoctoral Fellow Prevention Prevention strategy RNA Recurrence Research Research Personnel Research Support Resource Sharing Risk Scientist Screening for cancer Signal Transduction Sleeplessness Strategic Planning Therapeutic Training Activity Training Programs Training and Education Treatment outcome Uncertainty United States National Institutes of Health Vaccination Vision Writing anticancer research base cancer education cancer prevention cancer risk cancer stem cell care delivery career career development community engagement community setting dashboard electronic cigarette use epigenomics ethnic minority population fighting first-in-human follow-up improved infection related cancer innovation member metastatic process molecular imaging patient oriented premalignant prevent programs prospective screening stem stem cell biology survivorship targeted treatment theranostics translational research program tumor tumor heterogeneity tumor immunology

项目摘要

HIV infection is associated with a greatly increased risk for the development of non-Hodgkin lymphoma (NHL). Nearly all AIDS-related lymphomas (ARL) are of B cell origin. Two major mechanisms are believed to contribute to the genesis of ARL: 1) loss of immunoregulation of EBV+ B cells resulting from impaired T cell function, and 2) chronic B cell activation leading to DNA-modifying events that contribute to oncogene mutations/translocations. HIV infection has long been known to be associated with chronic, polyclonal B cell activation and, more recently, has been associated with microbial translocation. Recently, it has been shown that HIV, inflammatory cytokines and LPS can induce a B-regulatory cell (Breg) phenotype. Bregs are CD24+CD38+ B cells with regulatory functions that secrete IL10. Moreover, we have observed that Bregs are elevated prior to ARL development and that these cells express Program cell Death Ligand (PDL1). Additionally, we have preliminary data showing that NHL and ARL cell lines secrete PDL1+ exosomes, which have been shown to have prognostic value in cancer: PDL1+ exosomes are elevated in the circulation of patients that are non-responders to immunotherapy. More importantly, we have observed that PDL1+ exosomes are detectable in plasma from ARL patients and that plasma levels of these exosomes decrease following treatment. Therefore, we propose that PDL1+ exosomes may be a good biomarker for ARL risk and/or prognosis, and that PDL1+ exosomes are induced by inflammatory cytokines and LPS, which are known to be elevated prior to the development of ARL and also are known to induce PDL1 expression, as well as the secretion of exosomes. In this study we propose studies to determine if: 1) inflammatory cytokines and/or LPS can induce the secretion of exosomes containing PDL1 or B7 receptors, 2) exosomes containing PDL1 and B7 receptors have the capability to regulate T cell function, including anti-tumor effector functions, and 3) in vivo levels of circulating PDL1+, PDL2+, CD80+, CD86+and CD40L+ exosomes are associated with levels of serum markers of microbial translocation and/or inflammatory cytokines, and if circulating exosomes are good biomarkers for ARL risk and prognosis. This project serves as a supplement to P30CA016042. UCLA Jonsson Comprehensive Cancer Center’s goal is to advance studies that aim to define cancer risk to inform prevention, treatment, and foster survivorship; decode initiation and evolution of cancer; understand individual cancers at unprecedented levels to improve patient treatment and outcomes; and harness the body’s immune system to control and treat cancer.

HIV感染与B细胞起源的非霍奇金淋巴瘤（NHL）的发展相关。 t细胞功能受损，分配给癌基因突变/易位。。在循环中，我们已经观察到PDL1+外泌体在血浆中可检测到来自ARL的专利和tasma水平，因此我们建议使用PDL1+外os骨。已知在ARL发展之前已升高，并已知诱导PDL1的表达，以确定：1）炎症性细胞因子/或LPS。受体，2）含有PDL1和B7受体的外泌体具有调节T细胞功能，包含抗肿瘤效应功能的能力，3）3）在体内循环PDL1+，CD80+，CD86+和CD40L+外Nessomes的体内水平与水平与水平相关微生物sranslosial和/或炎症的细胞因子的标记，以及循环的外泌体是ARL风险和预后的疾病和癌症的进化；