Biomarkers of Kaposi sarcoma recrudescence in Zambia

摘要 卡波西肉瘤（KS）仍然是撒哈拉以南非洲地区的一种高度流行的恶性肿瘤。抗病毒 抗逆转录病毒疗法（ART）和相关的免疫重建与 KS在美国HIV感染人群中的患病率，但ART对撒哈拉以南地区KS的影响 非洲就不那么清楚了。在赞比亚，即使抗逆转录病毒疗法的规模扩大，KS仍然是第二常见的 成年男性的癌症对于女性来说，这是第三个最常见的。此外，治疗 化疗加抗逆转录病毒疗法与复发率高达50%的那些有 完整的回答。本申请的总体目标是鉴定流行性KS的标志物 复发和/或持续缓解的个体，具有初始完全消退， 化疗后的病变。我们假设，所有症状完全消退的个体， 化疗后的病变在免疫和病毒因素方面会有差异， 预测KS再发展和/或持续缓解的预后价值。我们将测试我们的 通过纵向表征先天性，体液和细胞免疫反应， KSHV和比较个人的经验，复发那些谁没有。的识别 这些缓解后结果的生物标志物将使得能够选择需要更长时间治疗的患者。 随访期、需要维持治疗的患者和需要二线治疗的患者 化疗通过我们的拟议活动，我们将改善艾滋病毒+的长期成果。 以前有KS的人，因此复发的风险很高。这将最终告知 努力更好地了解KS发病机制和开发新的干预策略。

ABSTRACT Kaposi's sarcoma (KS) remains a highly prevalent malignancy in sub-Saharan Africa. Antiretroviral therapy (ART) and associated immune reconstitution has been correlated with a dramatic decline in the prevalence of KS in the US HIV infected population, but the impact of ART on KS in sub-Saharan Africa is less clear. In Zambia, even with the scale up of ART, KS remains the second most common cancer among adult men. For women, it is the third most common. Furthermore, treatment with chemotherapy plus ART is associated with recurrence rates of up to 50 percent in those that have a complete response. The overall objective of this application is to identify markers of epidemic KS recurrence and/or sustained remission in individuals that have an initial complete regression of lesions upon chemotherapy. We hypothesize that individuals with complete regression of all the lesions after chemotherapy will have differences in immunological and viral factors that have prognostic value for predicting KS re-development and/or sustained remission. We will test our hypothesis by longitudinally characterizing innate, humoral, and cellular immune responses against KSHV and comparing individuals that experience recurrence to those who do not. The identification of these biomarkers of outcome after remission will enable the selection of patients that require a longer follow up period, those that require maintenance therapy, and those that require second line chemotherapy. From our proposed activities, we will improve the long-term outcomes of HIV+ individuals that have had KS before and hence at high risk of recurrence. This will ultimately inform efforts to better understand KS pathogenesis and develop novel interventional strategies.