Biomarkers of Kaposi sarcoma recrudescence in Zambia

赞比亚卡波西肉瘤复发的生物标志物

基本信息

批准号：
10871751
负责人：
Owen Ngalamika
金额：
$ 9.99万
依托单位：
UNIVERSITY OF ZAMBIA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2024-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10871751
关键词：
AIDS related cancer Acceleration Age Aging Biological Biological Aging Biological Markers CD28 gene CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes CD8B1 gene Cancer Control Cardiovascular Diseases Cardiovascular system Cell Aging Cell Count Cessation of life Chronology Cohort Studies DNA Damage Development Disease Disease remission Effector Cell Environmental Exposure Epidemic Ethics Etiology Exposure to Failure Flow Cytometry Frequencies Funding HIV HIV Infections HIV Seropositivity HIV/AIDS High Prevalence Histologic Human Herpesvirus 8 Immune Immune system Immunity Immunologic Markers Immunosuppression Incidence Individual Infection Infectious Agent Inflammaging Interleukin-1 Interleukin-6 Kaposi Sarcoma Lytic Phase Malignant Neoplasms Measures Mentors Mentorship Parents Participant Pathologist Persons Physiological Plasma Population Premature aging syndrome Process Recording of previous events Recrudescences Recurrence Reporting Research Design Risk T memory cell T-Lymphocyte TNF gene Time Treatment Failure United States National Institutes of Health Universities Viral Antigens Viral Cancer Viral Load result Virus Diseases Zambia age related aged antiretroviral therapy body system cancer cell cancer risk cell injury chemotherapy disorder risk emerging adult epidemic potential exhaustion follow-up high risk human old age (65+)immune checkpoint immunosenescence infection risk laboratory experiment latent infection lecturer medical schools mental function neurovascular programmed cell death protein 1 psychologic recruit responsible research conduct seropositive sex therapeutic target

项目摘要

Abstract Aging is a natural process that may come in several forms including psychological, chronological, and biological. Biological aging is associated with the development of many conditions including neurovascular, cardiovascular, and cancer. Among the hallmarks of cancer development is failure of the immune system to recognize and/or kill cancer cells. The aspect of the immune system important in cancer control is T cell immunity. Multiple factors including environmental exposure and HIV infection have been shown to promote premature aging of the immune system. Hence, malignancies and other old-age-related conditions have a higher prevalence among younger people living with HIV. In a current study on biomarkers associated with recurrence of HIV-associated Kaposi sarcoma upon successful treatment with chemotherapy, we have observed many age-associated effects on the T cell population. We have observed that there is a high expression of the marker of immune exhaustion (PD1) on CD8 T cells, which suggests a more aged T cell population in these individuals despite them having a relatively younger median age of about 40 years. The main objective of this study is to investigate T cell aging in individuals previously treated for an HIV- associated malignancy (Kaposi Sarcoma). These individuals will be compared to age- and sex-matched controls who are HIV+ and HIV-. Also, HIV+ controls will be further compared with HIV- controls. We will explore this through the following specific aims: 1) Recruit and mentor Dr. Chibamba Mumba to study HIV- associated premature aging in individuals with an HIV/AIDS-associated malignancy; 2) Recruit cases with a history of HIV-associated KS and KSHV-seropositive asymptomatic controls; 3) Compare the proliferative capacity and markers of T cell senescence, immune exhaustion, and Inflammaging in cases versus controls. Overall, this study will investigate the effect of HIV on premature aging of T cells, and how this may predispose to development of cancer.

抽象的衰老是一个自然过程，可能会以多种形式出现，包括心理，年代和生物。生物衰老与许多疾病的发展有关，包括神经血管，心血管和癌症。癌症发展的标志是免疫系统未能识别和/或杀死癌细胞。免疫系统在癌症控制中重要的方面是T细胞免疫。已显示包括环境暴露和HIV感染在内的多种因素可以促进免疫系统过早衰老。因此，恶性肿瘤和其他与老年有关的情况有艾滋病毒感染的年轻人的患病率更高。在当前关于与生物标志物相关的生物标志物的研究中与HIV相关的Kaposi肉瘤复发后，在化学疗法成功治疗后，我们已经观察到许多与年龄相关的对T细胞种群的影响。我们观察到有一个高 CD8 T细胞上免疫耗竭标记（PD1）的表达，这表明T细胞更老尽管这些人的人口中位年龄相对较小，但大约40岁。这这项研究的主要目的是研究先前治疗过HIV-的个体的T细胞衰老相关的恶性肿瘤（Kaposi肉瘤）。这些人将与年龄和性别匹配艾滋病毒+和艾滋病毒的控制。同样，将HIV+对照与HIV对照组进行比较。我们将通过以下特定目的探讨这一点：1）招募和指导Chibamba Mumba博士研究HIV- 患有艾滋病毒/艾滋病相关的恶性肿瘤的个体中相关的过早衰老； 2）招募案件与HIV相关的KS和KSHV剧本无症状控制的历史； 3）比较增生性 T细胞衰老，免疫疲劳和炎症的能力和标记控件。总体而言，这项研究将研究HIV对T细胞过早衰老的影响，以及如何可能易于发展癌症。