Intratumoural microbiota: a new frontier in cancer development and therapy

Abstract

Human microorganisms, including bacteria, fungi, and viruses, play key roles in several physiological and pathological processes. Some studies discovered that tumour tissues once considered sterile actually host a variety of microorganisms, which have been confirmed to be closely related to oncogenesis. The concept of intratumoural microbiota was subsequently proposed. Microbiota could colonise tumour tissues through mucosal destruction, adjacent tissue migration, and hematogenic invasion and affect the biological behaviour of tumours as an important part of the tumour microenvironment. Mechanistic studies have demonstrated that intratumoural microbiota potentially promote the initiation and progression of tumours by inducing genomic instability and mutations, affecting epigenetic modifications, promoting inflammation response, avoiding immune destruction, regulating metabolism, and activating invasion and metastasis. Since more comprehensive and profound insights about intratumoral microbiota are continuously emerging, new methods for the early diagnosis and prognostic assessment of cancer patients have been under examination. In addition, interventions based on intratumoural microbiota show great potential to open a new chapter in antitumour therapy, especially immunotherapy, although there are some inevitable challenges. Here, we aim to provide an extensive review of the concept, development history, potential sources, heterogeneity, and carcinogenic mechanisms of intratumoural microorganisms, explore the potential role of microorganisms in tumour prognosis, and discuss current antitumour treatment regimens that target intratumoural microorganisms and the research prospects and limitations in this field.

Microbiome and cancer: from mechanistic implications in disease progression and treatment to development of novel antitumoral strategies

“…In essence, the influence of locally resident microbiota or intratumor microbiota on cancer therapy remains inadequately explored ( 115 ). Although the roles of certain locally resident or intratumor bacteria have been confirmed in select cases, the majority of studies have focused on gut-related scenarios.…”

Deciphering the Puzzle: Literature Insights on Chlamydia trachomatis-Mediated Tumorigenesis, Paving the Way for Future Research

“…Initially, it was thought that the tumor microenvironment, besides the tumor cells, comprised all the immune cells, chemokines, cytokines, and other molecules or cells present in the local environment. Currently, thanks to the advancements in next-generation sequencing and bioinformatic technologies, researchers have found new evidence regarding the microbiome’s role in modulating the tumor phenotype in some cancers, as well as modulating growth, inflammation, the immune system response, genome instability, and therapy resistance [ 38 , 40 , 41 ]. In 2022, the hallmarks of cancer were updated by Hanahan adding other factors that could influence the tumor, including polymorphic microbiomes [ 12 ].…”

“…Indeed, several studies reported that changes in tissue-specific microbiota are related to malignant transformation in these tissues [ 38 , 43 , 44 , 45 , 46 ]. It was demonstrated that some bacteria, such as Fusobacterium nucleatum , interfere with some molecular pathways involved in tumorigenesis, triggering the invasiveness potential of the cells, through modifications in cell–cell adhesion driving the epithelial-to-mesenchymal transition (EMT) process, which represents an important step in some physiological processes and in tumorigenesis [ 41 , 47 ]. In detail, a Fusobacterium nucleatum adhesin named FadA can bind to E-cadherin on tumor cells of the gut epithelium, modulating E-cadherin/β-catenin signaling, which results in more available molecules of β-catenin, triggering the EMT process leading to the invasiveness potential of the cells and ultimately increasing some oncogenes expression [ 48 , 49 ].…”

“…Other researchers have identified mechanisms linking bacterial migration with the formation of a premetastatic niche in the liver in colorectal cancer, which is an initial step of metastasis formation [ 50 ]. In addition, in recent years, researchers have uncovered microbial presence not only within organs once believed to be sterile, including the bladder, prostate, and uterus, but also within solid tumors, such as colorectal and ovarian tumors [ 39 , 41 , 51 , 52 ]. It is clear that microbiome alterations in the gynecological tract, as in the gastrointestinal tract, could lead to molecular signaling modulation driving inflammatory milieu and triggering oncogenesis [ 53 , 54 , 55 ].…”