Impact of HIV on the Tumor Microenvironment

HIV对肿瘤微环境的影响

基本信息

批准号：
10398014
负责人：
BLOSSOM A DAMANIA
金额：
$ 38.72万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10398014
关键词：
AIDS related cancer AIDS/HIV problem Accounting Acquired Immunodeficiency Syndrome Acute Address Affect Africa South of the Sahara Age B-Cell Development B-Cell Lymphomas Bacterial Translocation CD4 Lymphocyte Count Cancer Etiology Cause of Death Cells Chronic Development Disease Dose Elderly Epstein-Barr Virus Infections General Population HIV HIV Infections HIV Seronegativity HIV Seropositivity Human Herpesvirus 4 Human Herpesvirus 8 Immunosuppression Incidence Individual Infection Inflammation Kaposi Sarcoma Life Lymphoma Lymphoma cell Lymphomagenesis Malawi Malignant Neoplasms Non-Hodgkin&apos s Lymphoma Oncogenic Viruses Pathogenesis Persons Population Proteins Reporting Risk Role Time Transgenic Model Tumor Angiogenesis Tumorigenicity United States Viral Viral Cancer Viral Proteins angiogenesis antiretroviral therapy cohort high risk humanized mouse in vivo mortality mouse model nef Protein neoplasm registry novel primary effusion lymphoma response tumor tumor growth tumor microenvironment tumor progression tumorigenesis virus related cancer

项目摘要

Project Summary Abstract Cancer is the leading cause of death in HIV-infected individuals on combination antiretroviral therapy (cART) in the United States and globally. This is because people infected with HIV can expect a near normal life on cART and overall mortality is determined by the same diseases as in the general population. Nevertheless, certain cancers occur much more frequently in HIV-infected individuals than in HIV-negative persons. These cancers include the AIDS-defining cancers, Kaposi sarcoma (KS) and a variety of lymphomas, including primary effusion lymphoma (PEL), which is associated with infection with Kaposi's sarcoma-associated herpesvirus and non-Hodgkin lymphomas, which are associated with infection by Epstein-Barr virus. In fact, KS is the leading cancer in the HIV-positive population today. Furthermore, as the HIV-positive cohort ages they are at an increasing risk of developing both AIDS-defining cancers (ADCs) as well as non-AIDS defining cancers (NADCs). This application is in response to RFA-CA-17-030 on HIV/AIDS and the Tumor Niche. We propose to understand the impact of HIV infection on the microenvironment that surrounds the ADCs, Kaposi sarcoma and non-Hodgkin lymphoma. We will investigate the impact of HIV viral proteins on tumor progression and angiogenesis of ADCs using novel mouse models of pathogenesis and tumorigenesis. We will also explore the mechanisms for the increased rate of development of cancers in the HIV infected population.

项目摘要摘要癌症是抗逆转录病毒疗法（CART）的HIV感染个体死亡的主要原因（CART）在美国和全球。这是因为感染了艾滋病毒的人可以期待几乎正常的生活购物车和整体死亡率取决于与普通人群相同的疾病。尽管如此，某些癌症在艾滋病毒感染者中比在艾滋病毒阴性的人中更频繁。这些癌症包括定义的癌症，Kaposi肉瘤（KS）和各种淋巴瘤，包括一级积液淋巴瘤（PEL），与Kaposi肉瘤相关的感染有关疱疹病毒和非霍奇金淋巴瘤与爱泼斯坦 - 巴尔病毒感染有关。实际上， KS是当今HIV阳性人群中的主要癌症。此外，作为HIV阳性队列年龄他们越来越有发展艾滋病定义癌症（ADC）的风险以及定义的非援助癌症（NADCS）。该应用是响应于HIV/AIDS和肿瘤生态位的RFA-CA-17-030。我们建议了解HIV感染对ADC围绕ADC的微环境的影响，Kaposi sarcoma 和非霍奇金淋巴瘤。我们将研究HIV病毒蛋白对肿瘤进展的影响使用新型的发病机理和肿瘤发生的小鼠模型对ADC的血管生成。我们还将探索艾滋病毒感染人群中癌症发育率提高的机制。