The role of intratumoral microbiota in the development of cancer. (IMAGE)
Caption
The role of intratumoral microbiota in the development of cancer. (A) Tissue invasion and metastasis. Bacteria may enter the tumor microenvironment by breaching mucosal barriers (e.g., in the esophagus, lungs, colon, and cervix), by invasion of adjacent tissues, or through hematogenous dissemination (e.g., from the oral cavity or intestinal tract). Once present within tumors, microbial communities may interact with tumor cells, stromal elements, and immune cells through several mechanisms that may influence tumor initiation, growth, and treatment response. (B) Genome instability and mutation. Intratumoral bacteria may contribute to genomic instability through the production of toxins, reactive oxygen species, and other metabolites capable of inducing DNA damage. These processes can promote mutations, interfere with DNA repair mechanisms, and contribute to tumor heterogeneity. (C) Epigenetic modification. Microbial metabolites and signalling molecules may influence gene regulation through epigenetic mechanisms, such as DNA methylation, histone modification, and changes in chromatin structure, thereby altering tumor cell behaviour without modifying the underlying DNA sequence. (D) Tumor-promoting inflammation. Microbial components may activate innate immune receptors, such as Toll-like receptors, triggering signalling pathways, including NF-κB, and stimulating the production of inflammatory mediators. (E) Avoiding immune destruction. Chronic inflammation may promote tumor growth, angiogenesis, and the recruitment of tumor-supportive immune cell populations. Interactions between intratumoral bacteria and immune cells may contribute to the development of an immunosuppressive microenvironment. Modulation of T cells, natural killer cells, macrophages, and dendritic cells may reduce effective anti-tumor immune responses and allow tumor cells to evade immune-mediated elimination. (F) Metabolic regulation. Bacterial metabolism may alter the availability of nutrients and metabolites within the tumor microenvironment, influencing tumor cell metabolic pathways and supporting cellular adaptation to the metabolic constraints of the tumor niche. Microbial signalling may affect cell adhesion, epithelial–mesenchymal transition, and cytoskeletal organisation, potentially enhancing tumor cell motility and invasiveness and facilitating metastatic spread. Together, these processes illustrate how intratumoral microbiota may influence multiple aspects of tumor biology and may contribute to the complex microenvironment observed in certain cancers.
Credit
Cancer Biology & Medicine
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