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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.

摘要