Cancer Center Support Grant

患有艾滋病毒和宫颈癌的妇女更有可能复发和复发宫颈癌。治疗因素可能是艾滋病毒携带者风险增加的原因，但免疫抑制的肿瘤环境也可能是一个关键的和可改变的因素。我们已经开发了非侵入性分析方法来表征美国和博茨瓦纳患者的肿瘤微环境，这将使我们能够检验免疫抑制微环境是HIV相关宫颈癌的特征的假设。我们建议扩大博茨瓦纳和美国之间的合作，收集宫颈癌拭子，用于两个地点的序列TCR测序和微生物组分析。我们推测，我们在休斯顿患者中描述的免疫抑制微生物群可能也存在于博茨瓦纳的宫颈癌女性患者中。此外，我们假设HIV患者宫颈癌患者的T细胞多样性较低，HIV患者的克隆性T细胞扩增可能受到损害，HPV反应性克隆可能较少，这些变化可能是导致存活率下降的原因。为了实现这一目标，我们提出了以下具体目标：具体目标#1：确定博茨瓦纳宫颈癌患者体内乳杆菌的丰度及其与治疗反应和艾滋病毒状况的关系。具体目标#2：通过在基线和放射治疗5周后进行TCR测序来评估免疫激活。这些发现可能直接导致微生物区系干预，旨在改善HIV阳性宫颈癌患者的反应。为了确定广泛相关且最有可能成功的干预措施，需要深入了解感染和不感染艾滋病毒患者的微生物群和抗肿瘤免疫的关键要素。通过利用现有的合作和已建立的工作流程，我们可以在了解肿瘤微生物组在感染和不感染艾滋病毒的宫颈癌患者中的作用方面取得重大进展。

Women with HIV and cervical cancer are more likely to suffer a relapse and recurrence of cervical cancer. Treatment factors may contribute to this elevated risk for women with HIV, but an immunosuppressive tumor environment may also be a critical and modifiable factor. We have developed non-invasive assays to characterize the tumor microenvironment in patients in the US and Botswana which will enable us to test the hypothesis that an immunosuppressive microenvironment characterizes HIV associated cervical cancers. We propose to expand the collaboration between Botswana and the US, collecting cervical cancer swabs for serial TCR sequencing and microbiome analysis in both sites. We hypothesize that the immunosuppressive microbiome that we have characterized in Houston patients may also be present in women with cervical cancer in Botswana. Additionally, we hypothesize that less diversity is present in T-cells from cervical cancers in patients with HIV, that clonal T-cell expansion may be impaired in patients with HIV, fewer HPV reactive clones may be present and that these changes may account for reduced rates of survival. To accomplish this, we propose the following specific aims: Specific Aim #1: Determine the abundance of Lactobacillus inners in patients with cervical cancer in Botswana and its associated with treatment response and HIV status. Specific Aim #2: Assess immune activation through TCR sequencing performed at baseline and after 5 weeks of radiation. These findings may lead directly to microbiota interventions aimed at improving response in HIV positive cervical cancer patients. To identify interventions which are broadly relevant and are mostly likely to be successful, a deep understanding of the critical elements of the microbiome and anti-tumor immunity in patients with and without HIV is needed. By leveraging an existing collaboration and established workflow, we can make significant progress in understanding the role of the tumor microbiome in cervical cancer patients with and without HIV