Biomarkers of Kaposi sarcoma recrudescence in Zambia

摘要 衰老是一个自然的过程，可能以几种形式出现，包括心理，时间顺序， 生物学上的生物老化与许多疾病的发展有关，包括神经血管， 心血管疾病和癌症。癌症发展的标志之一是免疫系统无法 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 免疫力包括环境暴露和艾滋病毒感染在内的多种因素已被证明可以促进 免疫系统的过早老化。因此，恶性肿瘤和其他与老年有关的疾病有一个共同点， 年轻艾滋病毒感染者的流行率较高。在目前的一项研究中， HIV相关的卡波西肉瘤在化疗成功后复发，我们 观察到许多与年龄相关的T细胞群的影响。我们观察到， CD 8 T细胞上免疫衰竭标志物（PD 1）的表达，这表明T细胞更加老化 尽管这些人的中位年龄相对较年轻，约为40岁，但他们的人口仍然很少。的 本研究的主要目的是研究既往接受过HIV治疗的个体的T细胞老化， 相关恶性肿瘤（卡波西肉瘤）。这些人将与年龄和性别匹配的 HIV阳性和HIV阴性的对照组。此外，将进一步比较HIV+对照与HIV-对照。我们将 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- 与HIV/AIDS相关的恶性肿瘤患者的相关性早衰; 2）招募 HIV相关KS和KSHV血清阳性无症状对照的病史; 3）比较增殖性KS和KSHV血清阳性无症状对照的病史。 与对照组相比， 对照总的来说，这项研究将调查艾滋病毒对T细胞过早老化的影响，以及这种影响是如何产生的。 可能导致癌症的发生。

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.