Bacteria in cancer unmasked

Researchers at the Netherlands Cancer Institute have compiled a detailed catalog of bacteria living in cancer metastases. Having analyzed over 4000 tumors, they shed light on the diversity of these co-inhabitants and how they might interact with cancer cells and their surroundings. For example, certain bacteria were linked to a worse response to immunotherapy. This study paves the way to a better understanding of how bacteria help or hinder cancer (therapy), and how we can use this to patients' advantage. The researchers published their findings today in the scientific journal Cell.

Billions of microorganisms live on and in our bodies: bacteria, viruses, and yeasts-our microbiome. We need them, and they need us. Bacteria help us digest our food, for example, and cooperate with our immune system in the fight against pathogens. Gut bacteria in particular have been extensively studied, including in the context of cancer, such as how they can influence the effectiveness of immunotherapy and chemotherapy.

Metastases

But these tiny co-inhabitants also live outside the gut and are also found in tumors. Thanks to new techniques, researchers are getting better at discovering which microbes they are. But how bacteria get to a tumor, and what exactly they do there, remains largely unknown, making it unclear how important they are to cancer and the effect of treatments.

26 cancer types

Because many patients eventually pass away from cancer metastases, which are targeted by many treatments, the research groups of Emile Voest and Lodewyk Wessels took a closer look at these metastases. After all, little was known about bacteria in these tumors. Together with their colleagues at, among others, the Netherlands Cancer Institute and Oncode Institute they have now mapped which bacteria are present in cancer metastases. Both groups are part of Oncode Institute.

The researchers analyzed the code of the DNA present in tissue from more than 4,000 metastases of 26 types of cancer. In that genetic material, you can see not only which human cells are present, but also which bacteria-because these also have DNA. For this purpose, they used clinical information and DNA data generated by Hartwig Medical Foundation.

A family tree of all the different bacteria found in metastatic tumors, and how they are related to one another. The inner ring depicts the degree to which bacteria need oxygen. Red ones require oxygen, green ones thrive in locations without. Purple ones reflect bacteria with a thick cell wall (gram positive), pink ones have a thin wall (gram negative).

Terabytes

With that unimaginably large mountain of information (400 terabytes), they used computer power to figure out which bacteria congregate in which places (see figure). This required a lot of clever programming, as there is relatively little bacterial DNA in such a piece of tissue.

"Surprisingly, it's not just metastases from colon cancer that contain a lot of bacteria," says researcher Thomas Battaglia. One might expect that, especially because most of our bacteria reside in the gut, from where they could travel elsewhere in the body as a tumor metastasizes. "The exact bacteria present in a metastasis are strongly related to the location of the metastasis in the body, the conditions there, and the cancer type."

Therapy response

They also discovered a link between bacteria and therapy efficacy. Patients with lung cancer and Fusobacterium in their metastasis, for example, saw a worse response to immunotherapy than peers for whom that same bacteria was not found. Thomas: "We also noted that a more diverse bacterial community correlated with more active adjacent tumor cells."

"Our work paves the way for exploring new forms of treatments, such as treatment against bacteria that might help the tumor," co-author Iris Mimpen says. "It helps us understand how the complex environment of tumors works, an environment in which all kinds of cells-including bacteria-cohabitate and influence each other."

This research was financially supported by the AVL Foundation, KWF Dutch Cancer Society, and Oncode Institute.

Emile Voest groupLodewyk Wessels group

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