Review explores roles, mechanisms and applications of intra-tumoral microbiota in cancers

Numerous studies have demonstrated a strong link between the human microbiome and the progression of various diseases, including obesity, diabetes, hypertension, and malignant tumors. A 2018 study attributed 13% of global cancer incidence to microorganisms.

Intra-tumoral microorganisms (those residing within tumors) have been reported in a variety of major cancers and are closely associated with tumor type, initiation, progression, immune regulation, and therapeutic outcome.

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A recent review published in the Genes & Diseases journal by researchers from the Army Medical University, Key Laboratory of Minimally Invasive Surgery and Precision Treatment for Breast Cancer of Chongqing Municipal Health Commission, Third Affiliated Hospital of Chongqing Medical University, and Chongqing Medical University provides an overview of the hallmarks, roles, molecular mechanisms, and clinical applications of intra-tumoral microbiota in multiple human cancers.

Microbiome signatures

The review begins by describing the constituents of the intra-tumoral microbiome, including bacterial, viral, fungal, and parasitic signatures in various cancers, such as breast, lung, prostate, pancreatic, gastric, ovarian, and others. It then elucidates the mechanisms through which the intra-tumoral microbiome influences the initiation and progression of cancers: i) promoting genome integration and DNA damage, ii) activating oncogenic signaling pathways, and iii) modulating the tumor immune microenvironment.

The unique microbial signatures found in tissue and blood within and between most major cancer types, along with the tumor tissues, help distinguish normal tissue from cancerous ones, underscoring their potential diagnostic and prognostic value. For example, F. nucleatum has been shown as both a potential diagnostic and prognostic biomarker in cervical carcinoma.

Furthermore, the tumor microbiota may significantly impact toxicity and regulate the efficacy of cancer therapies, including chemotherapy, immunotherapy, and radiation therapy. While intra-tumoral microbiota generally suppress the immune response and promote cancer progression, a few have been shown to enhance the efficacy of immunotherapy. For example, Bifidobacterium has been shown to promote local anti-CD47 immunotherapy in a mouse model of colon adenocarcinoma.

Mediating resistance

The tumor microbiota has also been implicated in conferring radio- and chemo-resistance in different tumors. The intra-tumoral bacteria Gammaproteobacteria mediate gemcitabine resistance in pancreatic cancer by producing cytidine deaminase, resulting in gemcitabine degradation. Lactobacillus iners induces chemo- and radio-resistance in cervical cancer by reprogramming metabolic signaling pathways.

Targeting the tumor microbiota appears to be a plausible strategy in cancer precision medicine. Several intra-tumoral microbiota, including Bifidobacterium, Salmonella, Clostridium, Listeria, and Escherichia coli, have been successfully used as therapeutic bacterial carriers for the delivery of cancer vaccines. Similarly, engineered E. coli and Salmonella have been shown to enhance the anti-cancer therapeutic response.

In conclusion, this review provides a comprehensive outlook of the role of tumor microbiota in various aspects of tumorigenesis and drug resistance, with insights into their underlying mechanisms, their potential as clinical biomarkers, and their role in precision medicine.