An Atlas of the Liver Cancer Microbiome
Liver cancer represents the third most common cause of cancer-related mortality, worldwide. Tissue-resident microbiomes have been recognized across many tumor entities to modulate cancer progression and therapy response. However, a comprehensive characterization of the intratumoral microbiome in primary and secondary liver cancer is lacking and its pathophysiological and clinical relevance remains unclear. To address this, we applied a spectrum of independent and complementary approaches on altogether 1,299 patient liver tissue specimens and 588 controls integrating four distinct patient populations to comprehensively characterize the intratumoral microbiome. Surveying the most common subtypes of primary and metastatic liver cancer, we found microbiome composition to be distinct between tumor subtypes. An additional meta-analysis of tumor transcriptomes showed similar microbial signatures of enrichment in hepatocellular carcinoma (HCC) across four independent patient populations. Moreover, we found the bacterial load in HCC to be linked with a strong proinflammatory immune response and bacteria to colocalize with macrophages, revealed by spatial analysis of HCC tissue sections. In an exploratory analysis of liver cancer patients treated surgically or systemically, we identified multiple bacterial species prognostic for overall survival or correlating with response to immune checkpoint blockade. Overall, our analyses highlight the potential of exploring the intratumoral microbiome for novel facets of liver cancer etiology, for patient stratification, prognosis and therapy.