Biomarkers of Kaposi sarcoma recrudescence in Zambia

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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.