Study interactions between lung microbiota and immune cells in NSCLC

研究 NSCLC 中肺微生物群与免疫细胞之间的相互作用

• 批准号: 10487123
• 负责人: Chen Zhao
• 金额: $ 42.24万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10487123
• 关键词: Aztreonam; Bacteria; Cells; Clinical Trials; Data; Environmental Risk Factor; Epithelial; Genes; Genetic Transcription; Goals; Immune; Inhalation; Lung; Lung Neoplasms; Manuscripts; Mesenchymal; Methods; Non-Small-Cell Lung Carcinoma; Oncogenic; Pathology; Pathway interactions; Patients; Plants; Prognosis; Route; Sampling; Spatial Distribution; T-Lymphocyte; Tumor Subtype; Writing; beta catenin; cell stroma; follow-up; lung cancer cell; lung microbiota; macrophage; microbiome; neoplastic cell; novel; pembrolizumab; preservation; safety and feasibility; safety testing; single cell sequencing; tertiary lymphoid organ; transcriptomics; tumor

We developed a novel spatial meta-transcriptomic analysis method to generate spatially resolved information on diverse host cells and bacteria in lung tumor samples. We discovered that bacterial burden was enriched in tumor cells compared to T cells, macrophages, other immune cells, and stroma. Bacterial load increased from tumor-adjacent normal lung and tertiary lymphoid structures to tumor cells to the airways, suggesting that intratumor bacteria derive from that route of entry. Expression of oncogenic beta-catenin and epithelial-mesenchymal transition pathway genes was strongly correlated with bacterial burden, as were tumor subtypes and environmental factors. These data provide missing information on the interactions of bacteria with lung cancer cells and accompanying transcriptomic changes, providing a rationale for reducing the local intratumor microbiome for patient benefit. We have submitted our manuscript. To follow up on our findings, we are currently developing a single-cell sequencing method to capture bacterial and host transcriptional information simultaneously. In addition, we are writing a clinical trial to test the safety and feasibility of combining inhaled aztreonam and pembrolizumab in patients with NSCLC.

我们开发了一种新的空间元转录组分析方法，以生成肺肿瘤样本中不同宿主细胞和细菌的空间分辨信息。我们发现，与T细胞、巨噬细胞、其他免疫细胞和基质相比，肿瘤细胞中的细菌负荷更丰富。细菌负荷从肿瘤邻近的正常肺和三级淋巴结构增加到肿瘤细胞到气道，表明肿瘤内细菌来自该进入途径。致癌β-连环蛋白和上皮-间质转化途径基因的表达与细菌负荷密切相关，肿瘤亚型和环境因素也是如此。这些数据提供了关于细菌与肺癌细胞相互作用以及伴随的转录组学变化的缺失信息，为减少局部肿瘤内微生物组以造福患者提供了依据。我们已经提交了手稿。为了跟进我们的发现，我们目前正在开发一种单细胞测序方法，以同时捕获细菌和宿主的转录信息。此外，我们正在撰写一项临床试验，以测试吸入性氨曲南和派姆单抗联合治疗NSCLC患者的安全性和可行性。