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Tumor Microbiome Appears to Vary With Cancer Type

NEW YORK – The bacterial community found in and around tumors can vary significantly by cancer type, new research suggests.

In a paper published in Science on Thursday, researchers from the Weizmann Institute of Science in Israel and other international centers set out to characterize the bacteria found in and around tumors from seven cancer types, including melanoma, breast, ovarian, lung, pancreatic, bone, and brain cancer.

Co-senior authors Ravid Straussman, a molecular cell biologist at the Weizmann Institute, and Noam Shental, a mathematician and computer science researcher at the Open University of Israel, and their colleagues noted that "characterization of the tumor microbiome has remained challenging because of its low biomass."

In an effort to take a closer look at these microbial communities, the team turned to 16S ribosomal gene sequencing and quantitative PCR to identify and quantify bacteria present in 1,010 tumor samples and more than 500 neighboring normal tissue samples. The samples were collected from patients at nine medical centers, and the researchers focused on 528 bacterial species found in the tumors in their analysis.

When they looked at the species and genera present in each tumor type, the investigators saw bacterial community collections that varied in tumors from one cancer and tumor subtype type to the next, with breast cancer-associated microbiomes appearing particularly diverse and genera-rich.

"The exploration of multiple tumor types with a single platform allowed us to compare different tumor types and uncover cancer type-specific microbial signatures," the authors reported. Even so, they noted that "despite a very large variation in taxa levels, certain tumor environments are enriched for common, relevant bacterial functional traits."

Using immunohistochemistry experiments, fluorescence in situ hybridization with 16S rRNA-targeting probes, and other pathology approaches, they showed that the majority of the microbes identified in the tumor samples were intracellular bacteria nestled within tumor and immune cells — a finding supported by follow-up testing on four freshly collected breast tumor samples.

"Our data do not establish whether intratumor bacteria play a causal role in the development of cancer or whether their presence simply reflects infections of established tumors," the investigators wrote, though "it is of interest to further explore the effects that intratumor bacteria may have on different phenotypes of cancer cells and on the immune system and its interactions with tumor cells."

While the metabolic capabilities of bacteria in the tumor-associated microbiomes appeared to offer clues about the clinical features of the tumor, including smoking-related features in a collection of non-small cell lung cancers, the team cautioned that further work will be needed to confirm and clarify such potential interactions.

In a corresponding perspectives article in Science, University of California San Francisco and Chan Zuckerberg Biohub researcher Peter Turnbaugh and Chloe Atreya, a hematology and oncology researcher at UCSF, said the findings "raise multiple important questions for future study."

While prior research has shown that bacteria and other microbes may appear on the surface of tumors, they explained, the presence of microbes within tumor cells has been less explored, particularly for cancers that occur in relatively "sterile" environments. 

"Achieving a comprehensive understanding of the tumor microenvironment is a daunting yet critical step toward an organism-wide mechanistic model of cancer progression and, if successful, may unlock the next wave of precision cancer diagnostics and therapeutics," Turnbaugh and Atreya wrote.