Georgetown University Lombardi Comprehensive Cancer Center Support Grant

人类免疫缺陷病毒(HIV)感染与多种类型的 癌症。联合抗逆转录病毒疗法(CART)对减少获得性 免疫缺陷综合征(艾滋病)-定义癌症和PLWH的老化，非艾滋病-定义 癌症(NADCs)已成为这一人群死亡的主要来源，这已被观察到 在全球各地。在NADC中，肺癌是PLWH的首要死亡原因。不是小的- 细胞肺癌(NSCLC)是最常见的肺癌类型，占所有肺癌的85% 案子。艾滋病毒感染仍然是非小细胞肺癌的独立危险因素，即使在调整了潜在的 令人困惑的因素，如吸烟。在NSCLC初诊时，PLWH比那些 没有感染艾滋病毒。与未感染艾滋病毒的患者相比，感染艾滋病毒的非小细胞肺癌患者 预后较差，中位总生存期为4-6个月。虽然收入差距很大， 癌症的治疗至少部分归因于预后不佳，感染艾滋病毒的患者 即使接受分期适当的治疗，非小细胞肺癌的预后也较差。虽然慢性 与艾滋病毒感染相关的炎症和免疫监视减少已被提出。 作为PLWH中肺癌发生和转移的潜在机制，是否和是否 HIV相关的全身免疫失调在多大程度上影响局部免疫反应 肿瘤微环境尚未得到充分评价。随着癌症免疫治疗的成功， 作为免疫检查点抑制剂治疗包括肺癌在内的各种癌症类型， 了解免疫系统和免疫系统之间的相互作用变得越来越重要。 通过全面分析肿瘤微环境中的局部免疫反应，研究肿瘤细胞。 非小细胞肺癌PLWH患者肿瘤免疫微环境的研究 非小细胞肺癌(NSCLC)--最常见的肺癌类型--将加深我们对艾滋病毒引发的肺的理解 癌症的发生和发展，使我们能够设计新的免疫治疗方法 专门为PLWH设计的。在这项研究中，我们建议询问抑制基因的表达 HIV相关肿瘤微环境中的免疫检查点和免疫细胞群 以及与HIV无关的非小细胞肺癌，利用多路成像质谱仪技术(Fluidigm， 美国)。我们还将评估肿瘤微环境中艾滋病毒感染的存在及其 使用RNAScope原位杂交对局部免疫反应的影响(美国ACDbio)。在漫长的岁月里 综上所述，本文的研究成果有可能为小说的发展奠定基础 慢性肝病和非小细胞肺癌的免疫治疗策略。

Human immunodeficiency virus (HIV) infection is linked with an increased risk of many types of cancers. With the effect of combination antiretroviral therapy (cART) on reducing acquired immunodeficiency syndrome (AIDS)-defining cancers and the aging of PLWH, non-AIDS-defining cancers (NADCs) have become a major source of mortality in this population, which has been observed across the globe. Among the NADCs, lung cancer is the leading cause of death in PLWH. Non-small- cell lung cancer (NSCLC) is the most common type of lung cancer comprising 85% of all lung cancer cases. HIV infection remains an independent risk factor for NSCLC even after adjusting for potential confounders such as smoking. At the time of initial diagnosis of NSCLC, PLWH are younger than those without HIV infection. Compared to those without HIV infection, HIV-infected patients with NSCLC have a poorer prognosis with median overall survival between 4-6 months. While disparities in receiving cancer treatment have been at least partly attributed to the poor prognosis, HIV-infected patients with NSCLC have poorer outcomes even when they receive stage-appropriate treatment. While chronic inflammation and decreased immune surveillance associated with HIV infection have been suggested as potential mechanisms of lung cancer initiation and metastatic progression in PLWH, whether and to which extent HIV-associated systemic immune dysregulation affects the local immune response in the tumor microenvironment has not been fully evaluated. With the success of cancer immunotherapy such as immune checkpoint inhibitor therapy in the treatment of various cancer types including lung cancer, it has become increasingly important to understand the interactions between the immune system and cancer cells by comprehensively profiling the local immune response in the tumor microenvironment. Elucidation of the tumor immune microenvironment in PLWH suffering from non-small-cell lung cancer (NSCLC) – the most common type of lung cancer – will deepen our understanding of HIV-driven lung cancer tumorigenesis and progression and allow us to devise novel immunotherapeutic approaches designed specifically for PLWH. In this study, we propose to interrogate the expression of inhibitory immune checkpoints and immune cell populations in the tumor microenvironment in HIV-associated and HIV-unassociated NSCLCs, utilizing multiplexed imaging mass cytometry technology (Fluidigm, USA). We will also evaluate the presence of HIV infection in the tumor microenvironment and its impacts on the local immune response using RNAscope in situ hybridization (ACDbio, USA). In the long term, the results of the study have the potential to lay the foundation for development of novel immunotherapeutic strategies in PLWH and NSCLC.