The Interaction between Intratumoral Microbiome and Immunity Is Related to the Prognosis of Ovarian Cancer.

Abstract

Microbiota can influence the occurrence, development, and therapeutic response of a wide variety of cancer types by modulating immune responses to tumors. Recent studies have demonstrated the existence of intratumor bacteria inside ovarian cancer (OV). However, whether intratumor microbes are associated with tumor microenvironment (TME) and prognosis of OV still remains unknown. The RNA-sequencing data and clinical and survival data of 373 patients with OV in The Cancer Genome Atlas (TCGA) were collected and downloaded. According to the knowledge-based functional gene expression signatures (Fges), OV was classified into two subtypes, termed immune-enriched and immune-deficient subtypes. The immune-enriched subtype, which had higher immune infiltration enriched with CD8+ T cells and the M1 type of macrophages (M1) and higher tumor mutational burden, exhibited a better prognosis. Based on the Kraken2 pipeline, the microbiome profiles were explored and found to be significantly different between the two subtypes. A prediction model consisting of 32 microbial signatures was constructed using the Cox proportional-hazard model and showed great prognostic value for OV patients. The prognostic microbial signatures were strongly associated with the hosts' immune factors. Especially, M1 was strongly associated with five species (Achromobacter deleyi and Microcella alkaliphila, Devosia sp. strain LEGU1, Ancylobacter pratisalsi, and Acinetobacter seifertii). Cell experiments demonstrated that Acinetobacter seifertii can inhibit macrophage migration. Our study demonstrated that OV could be classified into immune-enriched and immune-deficient subtypes and that the intratumoral microbiota profiles were different between the two subtypes. Furthermore, the intratumoral microbiome was closely associated with the tumor immune microenvironment and OV prognosis. IMPORTANCE Recent studies have demonstrated the existence of intratumoral microorganisms. However, the role of intratumoral microbes in the development of ovarian cancer and their interaction with the tumor microenvironment are largely unknown. Our study demonstrated that OV could be classified into immune-enriched and -deficient subtypes and that the immune enrichment subtype had a better prognosis. Microbiome analysis showed that intratumor microbiota profiles were different between the two subtypes. Furthermore, the intratumor microbiome was an independent predictor of OV prognosis that could interact with immune gene expression. Especially, M1 was closely associated with intratumoral microbes, and Acinetobacter seifertii could inhibit macrophage migration. Together, the findings of our study highlight the important roles of intratumoral microbes in the TME and prognosis of OV, paving the way for further investigation into its underlying mechanisms.