Intratumoral Microbiome Dynamics in Cancer Biology

The intratumoral microbiome, comprising bacteria, viruses, fungi and other microorganisms that reside within malignant tissues, has emerged as an integral component of the tumour microenvironment. Far from mere bystanders, these microbes interact dynamically with cancer cells and infiltrating immune populations to influence oncogenesis, tumour progression, metastatic potential and response to therapy. Intratumoral communities may promote genetic instability through microbial metabolites and genotoxins, activate oncogenic signalling pathways and sustain chronic inflammation. Conversely, certain microbial constituents can enhance antitumour immunity by stimulating innate sensors and recruiting lymphocytes. Spatial heterogeneity is a defining feature of intratumoral microbiota, with micro-niches of high microbial density often correlating with immunosuppressive niches and altered vascularity. Advances in high-resolution profiling have revealed that tumour-associated microorganisms can serve as biomarkers for prognosis, stratify patients for immunotherapy and represent novel therapeutic targets or drug-delivery vehicles. As multi-omics and imaging methods continue to refine our understanding, the intratumoral microbiome is poised to inform personalised cancer management on a global scale.

Research from Nature Portfolio

Recent studies have demonstrated that human leukocyte antigen molecules in glioblastoma tissues present bacterial peptides that are recognised by tumour-infiltrating lymphocytes. Such findings reveal cross-reactivity between microbial antigens and tumour epitopes, suggesting new avenues for personalised neoantigen vaccination strategies and adjuvant therapies in brain cancer. Another investigation employing spatial transcriptomics and single-cell RNA sequencing has mapped microbial communities within oral squamous cell carcinoma and colorectal cancer. This work uncovered organised micrometre-scale bacterial niches that coincide with regions of immunosuppression and low proliferation, and identified host–microbe interactions that drive cell invasion and myeloid recruitment. These insights elucidate how intratumoral microbes shape local cellular phenotypes and tumour architecture.

Intratumoral Microbiome Dynamics in Cancer Biology publication trend

The graph below shows the total number of articles in intratumoral microbiome dynamics in cancer biology across all publications each year (not limited to Nature Index journals).

Technical terms

Intratumoral microbiome: The community of microorganisms, including bacteria, fungi and viruses, that inhabit the interior of a tumour.

Tumour microenvironment: The surrounding cellular and extracellular milieu of a tumour, comprising immune cells, vasculature, stromal elements and matrix components.

Tumour-infiltrating lymphocytes (TILs): Lymphocytes that have migrated from the circulation into the tumour tissue and participate in immune surveillance.

Spatial transcriptomics: A set of techniques that measure gene expression profiles while preserving the spatial origin of each transcript within a tissue section.

Mycobiome: The fungal component of a microbiome, encompassing all fungal species present in a given environment, such as a tumour.

References

1. Intratumoral microbiota: roles in cancer initiation, development and therapeutic efficacy. Signal Transduction and Targeted Therapy (2023).
2. Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma. Nature (2023).
3. Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer. Nature (2022).
4. Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions. Cell (2022).
5. Association of Intratumoral Microbiota With Prognosis in Patients With Nasopharyngeal Carcinoma From 2 Hospitals in China. JAMA Oncology (2022).