Spatial Multi-omics Analysis of The Tumor Microenvironment in Colon Cancers

Spatial Multi-omics Analysis of The Tumor Microenvironment in Colon Cancers

Abstract
The colon harbors the bulk of the human microbiome, with numerous studies reporting microbiome alterations in colorectal cancer (CRC), with proposed mechanisms for several bacterial species in CRC tumorigenesis and response to therapy. However, the network of host-microbe interactions in CRC is highly complex owing to the multitude of microbial species and host cell-types residing within the tumor microenvironment (TME). Importantly, the spatial organisation of these interactions has remained enigmatic, as spatial information is lost in most next generation sequencing approaches. To better understand how microbe-host interplay impacts CRC development, we utilized multi-omics approach to dissect the spatial architecture of tumor, immune, and tissue-resident microbiome in primary CRC tissues. Using spatial transcriptomics, we show differential immune infiltration dynamics across CRC subtypes, and correlate that to tumors mutational profile. Furthermore, we developed new protocols to simultaneously profile and map host and tumor-resident microbiome in situ. This revealed intricate architecture and altered composition of microbiome and immune landscape inside the TME. Our multi-omics approach highlights the importance of coupling spatially resolved transcriptomics with scRNA-seq and microbiome profiling assays in analyses of the TME in colon tumors.