Intratumoural microbiota: a new frontier in cancer development and therapy Original paper

What was reviewed?

This review article explores the emerging role of intratumoral microbiota in cancer development and therapy. It focuses on the concept that tumor tissues, once thought to be sterile, actually host a variety of microorganisms, including bacteria, fungi, and viruses. These microorganisms are an integral part of the tumor microenvironment (TME) and significantly influence tumor behavior. The review addresses the potential sources of intratumoral microbiota, including mucosal invasion, adjacent tissue migration, and hematogenous spread. It examines how these microbial populations contribute to tumor initiation, progression, and metastasis through mechanisms such as genomic instability, inflammation, immune evasion, and altered metabolism. Additionally, the article discusses how manipulating the intratumoral microbiota may offer new strategies for cancer therapy, particularly in the context of immunotherapy.

Who was reviewed?

The article synthesizes research on the microbiota found in various cancers, providing an overview of studies that have identified specific microbial communities within tumor tissues. It reviews studies involving a range of cancer types, including lung, colorectal, liver, gastric, and pancreatic cancers. The focus is on how these microorganisms interact with host cells to influence tumor biology, immune responses, and treatment outcomes. Key microbial species, such as Fusobacterium nucleatum, Enterotoxigenic Bacteroides fragilis, and Helicobacter pylori, are discussed for their roles in carcinogenesis. The review also includes research on how microbial signatures in tumors can be used for cancer prognosis and how microbial interventions might be integrated into current therapeutic strategies.

Most important findings

The review highlights several critical findings on the role of intratumoral microbiota in cancer. Tumor tissues host distinct microbial populations, which vary by cancer type and stage. Bacteria like Fusobacterium nucleatum and Bacteroides fragilis have been linked to colorectal cancer and are shown to promote tumor growth by inducing DNA damage and inflammation. Additionally, the microbiota within tumors can influence the immune environment, often promoting immune evasion and inflammation that aids in cancer progression. Certain microbes, such as F. nucleatum, actively contribute to immune suppression by activating immune checkpoints or inducing immune cell dysfunction. The presence of specific microorganisms also affects the response to cancer treatments, particularly immunotherapy, with some microbiota enhancing the efficacy of therapies while others contribute to resistance. The review also emphasizes the potential of using microbiota manipulation as a therapeutic approach, with early-stage studies showing promise in targeting microbial communities to improve cancer outcomes.

Key implications

The review presents several important clinical implications for cancer treatment. Understanding the role of intratumoral microbiota could lead to new diagnostic biomarkers that predict cancer progression and therapy response based on microbial signatures. Moreover, interventions aimed at modifying the tumor microbiota, such as using probiotics, antibiotics, or immunotherapies targeting microbial populations, could become part of personalized cancer treatment regimens. Targeting the microbiota within the tumor microenvironment, particularly through immune modulation, could enhance the effectiveness of existing therapies, such as immune checkpoint inhibitors. However, further research is needed to fully understand the complex interactions between intratumoral microbiota and the host immune system, as well as the long-term effects of microbiota-targeted therapies in cancer patients.