Tumor tissue microorganisms are closely associated with tumor immune subtypes

Abstract

Studies have found that different immune subtypes are present in the same tumor. Different tumor subtypes have different tumor microenvironments (TME). This means that the efficacy of immunotherapy in actual applications will, therefore, have different results. Existing tumor immune subtype studies have mostly focused on immune cells, stromal cells, genes and molecules without considering the presence of microbes. Some studies have shown that microflora can strongly promote many gastrointestinal cancers. The microbiome has, therefore, become an important biomarker and regulatory factor of cancer progression and therapeutic responses. In addition, the presence of microflora can strongly regulate the host immune system, indirectly affecting tumor growth. Taken together, it is important to study the relationships that develop among tumor tissue microorganisms, tumor immune subtype, and the TME. In this study, correlations between microbial abundance, immune cell infiltration, immune gene expression and tumor immune subtype were studied. To accomplish this, tissue microorganisms and immune cell ratios with significant differences between the different cancers were obtained by comparing 203 gastric cancer and intestinal cancer samples. Two immune subtypes of intestinal samples were obtained by K-means clustering algorithm and tissue microorganisms, immune cell ratios and immune-related genes with significant differences between different immune subtypes were screened through Wilcoxon rank sum test. The results showed that Clostridioides difficile, Aspergillus fumigatus, Yarrowia lipolytica, and Fusarium pseudograminearum were all closely associated with the identified tumor immune subtypes. Our open-source software is freely available from GitHub at https://github.com/gutmicrobes/IMM-subtype.git.

Keywords: Gene expression profiling; Immune subtype; RNA-seq; Tissue microorganisms; Tumor microenvironment.