Tumor microbiome - an integral part of the tumor microenvironment

Abstract

The tumor microenvironment (TME) plays a significant role in tumor progression and cancer cell survival. Besides malignant cells and non-malignant components, including immune cells, elements of the extracellular matrix, stromal cells, and endothelial cells, the tumor microbiome is considered to be an integral part of the TME. Mounting evidence from preclinical and clinical studies evaluated the presence of tumor type-specific intratumoral bacteria. Differences in microbiome composition between cancerous tissues and benign controls suggest the importance of the microbiome-based approach. Complex host-microbiota crosstalk within the TME affects tumor cell biology via the regulation of oncogenic pathways, immune response modulation, and interaction with microbiota-derived metabolites. Significantly, the involvement of tumor-associated microbiota in cancer drug metabolism highlights the therapeutic implications. This review aims to summarize current knowledge about the emerging role of tumor microbiome in various types of solid malignancies. The clinical utility of tumor microbiome in cancer progression and treatment is also discussed. Moreover, we provide an overview of clinical trials evaluating the role of tumor microbiome in cancer patients. The research focusing on the communication between the gut and tumor microbiomes may bring new opportunities for targeting the microbiome to increase the efficacy of cancer treatment and improve patient outcomes.

Keywords: bacterial diversity; cancer; gut microbiota; treatment response; tumor microbiome; tumor microenvironment.

Figure 1

The role of tumor microbiome in cancer development and treatment. Proposed mechanisms by which the tumor microbiome affects tumorigenesis, cancer progression, and response to therapeutic agents include increased mutagenesis, regulation of oncogenes and oncogenic pathways, modulation of host immune response pathways, cancer drug metabolism, production of bacterial toxins and microbiota-derived metabolites. Mounting evidence from animal models and clinical studies revealed the association of tumor microbiome with clinicopathologic features, cancer treatment efficacy, metastatic potential, and cancer survival.

Figure 2

Specific intratumoral bacteria within different types of tumors. The presence of cancer type-specific bacteria within the tumor microenvironment was revealed mainly by 16S rRNA or metagenomic sequencing and via immunohistochemical and immunofluorescence detection methods.