Landscape of the intratumoral microbiota acting on the tumor immune microenvironment in LUAD and LUSC

Although the intratumoral microbiota has been discovered to have a close connection with tumor immunity, the specific role played by intratumoral microbiota in regulating the tumor immune microenvironment (TIME) of lung cancer remains largely unexplored. Here, we comprehensively investigated the association between intratumoral microbiota and the TIME in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). First, we found that intratumoral microbiota and host transcriptome profile significantly differed between LUAD and LUSC. Moreover, there were strong associations between the abundance of intratumoral microbes and the expression of host genes in both LUAD and LUSC. Furthermore, we found an association between intratumoral <i>Lachnoclostridium</i> and chemokine expression, suggesting a role for these species of microbiota in modulating tumor immunity. In addition, we found that tumors harbor distinct relative abundance of <i>Lachnoclostridium</i> presented variation in response to immunotherapy and sensitivity to potential drug candidates. Our study provided important insights into the regulation of intratumoral microbiota on the TIME in LUAD and LUSC, which may serve as a precursor for a hypothesis-driven study to better understand the causational relationship of intratumoral microbiota in lung cancer.<b>NEW & NOTEWORTHY</b> LUAD and LUSC exhibited significant differences in intratumoral microbiome and the TIME profile. The relative abundance of intratumoral <i>Lachnoclostridium</i> correlated with the tumor immune infiltration in both LUSC and LUAD. Intratumoral <i>Lachnoclostridium</i> impacted the patients' sensitivity to potential targeted drugs, especially in LUSC.