Dissection of Intratumor Microbiome-Host Interactions at Single-Cell Level in Lung Cancer

The intratumor microbiome, one of the hallmarks of cancer, plays a crucial role in cancer progression through interaction with the host. However, the underlying mechanisms remain poorly understood. Here we investigated the heterogeneity of host-microbiome interactions at the single-cell level by integrating six single-cell transcriptomic lung cancer datasets using single-cell analysis of host-microbiome interactions (SAHMI). Our findings indicate that primary tumor tissues display a high proportion of fungi-associated cells, whereas metastatic brain tissues predominantly feature bacteria-associated cells. A distinct distribution of fungal and bacterial taxa across various cell types was observed. Notably, the presence of specific bacteria significantly influences the transcriptome of resident host cells, including T cells and macrophages, by modulating pathways related to rRNA processing, cellular responses to stress and stimuli, and the metabolism of RNA and proteins. Finally, specific cell-associated bacteria are significantly correlated with clinical features, such as lung cancer stages and smoking frequency. These single-cell insights into microbiome-host interactions facilitate our understanding of lung cancer development and progression, offering potential microecological and diagnostic insights.