Study interactions between lung microbiota and immune cells in NSCLC

我们开发了一种新的空间元转录分析方法来生成关于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、其他免疫细胞和间质相比，肿瘤细胞中的细菌负荷更丰富。从肿瘤邻近的正常肺和第三淋巴样结构到肿瘤细胞到呼吸道的细菌负荷增加，这表明肿瘤内的细菌来自这一进入途径。致癌基因β-连环素和上皮-间充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。这些数据提供了有关细菌与肺癌细胞相互作用以及伴随的转录变化的缺失信息，为减少局部肿瘤内微生物群以造福患者提供了理论基础。我们已经提交了我们的手稿。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培溴珠单抗联合治疗非小细胞肺癌患者的安全性和可行性。

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.