Abstract
BACKGROUND: While the resident microbiome of tumors has been shown to be associated with the occurrence and progression of non-small cell lung cancer, there remains a significant knowledge gap in understanding the correlation between the microbial spectrum and immunity response to cancer therapy. In the case of lung adenocarcinoma (LUAD), the tumor microenvironment, encompassing a diverse array of microbes and immune cells, plays a crucial role in modulating therapeutic response. Towards comprehending the underlying mechanism, we present the microbe-immunity interactive networks to delineate the microbiota and immunity repertoires for two distinct molecular subtypes in LUAD. METHODS: We obtained multi-omics data of LUAD patients from the publicly available database. In this study, we conducted a systematic exploration of the microbial and immunological etiology of cancer prognosis, by integrating the microbiome, genome, transcriptome, and clinic data. The mutational signature analysis, transcriptome analysis, gene set enrichment analysis, and microbiota-immunity network analysis were performed. RESULTS: Based on the transcriptome repertories, we classified the patients into two molecular subtypes and observed that the overall survival of molecular subtype 2 (MS2) was notably shortened. We identified the microbial biomarkers in patients that distinguished between these molecular subtypes. The significant up-regulation of γδT and neutrophil in MS2, suggesting the inflammation augmentation and stimulation of γδT activation. What is more, the MS2 are characterized by a correlation network between microbiota biomarkers and γδT cell, which may contribute to suppression of anti-tumor immunity and poor overall survival. CONCLUSIONS: Our findings not only display the repertoires of tumor microbiota and immune cells, but also elucidate the potential contribution of the microbiota-immunity correlation network to unfavorable overall survival and therapeutic resistance, thereby exerting profound implications on future LUAD therapy.