Exploring the Role of Intratumor Microbiome in Lung Cancer Progression
The intricate relationship between the human microbiome and health has garnered increasing attention, particularly in the realm of cancer research. Recent findings indicate that the intratumor microbiome may significantly influence lung cancer, a leading cause of cancer-related deaths worldwide. A comprehensive study from a team of researchers at Tsinghua University has shed light on how microbial profiles within lung cancer tissues interact with single cells, potentially affecting tumor development and patient outcomes.
The research team undertook an extensive analysis, integrating six publicly available single-cell RNA sequencing datasets from 149 lung cancer patient samples. These samples included various tissue types--lung cancer lesions, adjacent normal tissues, and brain metastases. By employing the SAHMI tool, the researchers meticulously eliminated potential microbial contamination and batch effects during data integration, enabling them to accurately identify microbial sequences linked to individual host cells.
The study revealed that the composition of host cells varies throughout the progression and metastasis of lung cancer. Notably, the number of bacterial-associated cells was consistently higher than that of fungal-associated cells across all examined tissue types, including primary lung tumors, adjacent normal tissues, and metastatic sites. Interestingly, the proportion of fungal-associated cells was most elevated in primary lung cancer lesions, while bacterial-associated cells were more prevalent in brain metastatic tissues.
In addition to variations in cell composition, the research highlighted significant differences in the distribution of specific bacteria and fungi across various cell types within the lung cancer microenvironment. The presence of particular microbial species was shown to affect host cell gene expression, modulating several biological pathways linked to stress responses, RNA and protein metabolism, and cellular signaling.
Moreover, the analysis indicated that bacterial presence could influence communication between host cells, particularly T cell subtypes, leading to differential regulation in macrophages depending on their microbial associations. For instance, the presence of bacteria was linked to the upregulation of certain genes in macrophages, while fungal associations led to downregulation of others.
Furthermore, the study identified correlations between specific microorganisms and the smoking status of lung cancer patients. Variations in the abundance of various fungi were observed in relation to the type of lung tissue, with distinct patterns emerging in normal, primary, and metastatic cancer samples. These findings suggest that the intratumor microbiome not only plays a role in lung cancer development but may also reflect the patient's smoking history, a known risk factor in lung cancer.
This groundbreaking research underscores the complexity of interactions between the microbiome and host cells within the lung cancer microenvironment. By unraveling these intricate relationships at the single-cell level, scientists may gain new insights into the factors influencing cancer progression and prognosis. Ultimately, this knowledge could pave the way for personalized cancer therapies that take into account the unique microbiome profiles of individual patients, enhancing treatment efficacy in clinical settings.
In summary, the study offers a novel perspective on the role of the intratumor microbiome in lung cancer, highlighting its potential as both a biomarker and a target for innovative therapeutic strategies.