Impact of HIV on the Tumor Microenvironment

项目摘要摘要 在联合抗逆转录病毒疗法(CART)中，癌症是艾滋病毒感染者死亡的主要原因 在美国和全球范围内。这是因为感染艾滋病毒的人可以预期在接下来的日子里可以过上接近正常的生活。 CART和总死亡率是由与普通人群相同的疾病决定的。不过， 某些癌症在感染艾滋病毒的人中比在艾滋病毒阴性的人中更容易发生。这些 癌症包括定义艾滋病的癌症、卡波西肉瘤(KS)和各种淋巴瘤，包括 与卡波西肉瘤相关感染相关的原发性渗出性淋巴瘤(PEL) 疱疹病毒和非霍奇金淋巴瘤，与EB病毒感染有关。事实上, KS是当今HIV阳性人群中的主要癌症。此外，随着艾滋病毒阳性人群的年龄增长 他们患艾滋病定义癌症(ADC)和非艾滋病定义癌症(ADC)的风险越来越高 癌症(NADCs)。 这项申请是对关于艾滋病毒/艾滋病和肿瘤缝隙的RFA-CA-17-030的响应。我们建议 了解HIV感染对ADC、Kaposi肉瘤周围微环境的影响 和非霍奇金淋巴瘤。我们将研究HIV病毒蛋白对肿瘤进展和 利用新的小鼠发病机制和肿瘤发生模型研究自发性DC的血管生成。我们还将探索 艾滋病毒感染人群中癌症发展速度增加的机制。

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.