Biomarkers of Kaposi sarcoma recrudescence in Zambia

摘要 衰老是一个自然的过程，可能有几种形式，包括心理上的、时间上的和 生物学上的。生物衰老与许多疾病的发展有关，包括神经血管， 心血管疾病和癌症。癌症发展的特征之一是免疫系统不能 识别和/或杀死癌细胞。免疫系统在癌症控制中的重要方面是T细胞 豁免权。包括环境暴露和艾滋病毒感染在内的多种因素已被证明促进了 免疫系统过早老化。因此，恶性肿瘤和其他与老年有关的疾病 艾滋病毒携带者中年轻人的流行率更高。在一项最新的研究中发现，生物标记物与 HIV相关性Kaposi肉瘤的复发在化疗成功治疗后，我们有 观察到许多与年龄相关的对T细胞数量的影响。我们观察到有一个很高的 CD8 T细胞免疫耗竭标志物PD1的表达，提示T细胞老化 尽管这些人的年龄中位数相对较低，约为40岁，但这些人的人口比例仍然很高。这个 这项研究的主要目的是调查以前接受过艾滋病毒治疗的人的T细胞老化。 伴发恶性肿瘤(卡波西肉瘤)。这些人将被与年龄和性别匹配的人进行比较 控制谁是HIV和HIV-。此外，还将进一步将艾滋病毒控制与艾滋病毒控制进行比较。我们会 通过以下具体目标探索这一点：1)招募和指导Chibamba Mumba博士研究艾滋病毒- HIV/AIDS相关恶性肿瘤患者的相关早衰；2)招募有 HIV相关KS和KSHV血清阳性对照的病史；3)比较增殖期 病例对照中T细胞衰老、免疫衰竭和炎症的能力和标志物 控制。总而言之，这项研究将调查艾滋病毒对T细胞过早老化的影响，以及这是如何实现的 可能会导致癌症的发生。

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.