A new way to detect tumors: look for their microbes

Search for a picture of the tumor on Google, and you will likely end up with a group of brightly colored cancer cells against a dark background of healthy tissue. But for Jan Naronsky Haziza, a cancer biologist at the Weizmann Institute of Science in Israel, the picture looks very different. A tumor may also contain millions of microbes representing dozens of species.

“I think this is an ecosystem,” she said. “This means that the cancer cells are not alone.”

Scientists have long known that our bodies are home to microbes, but they tend to treat tumors as if they were sterile. However, researchers in recent years have put this concept to rest, showing that tumors are full of microbes.

In 2020, several research teams showed that tumors are home to a different mix of bacteria. and on Thursday, two studies The publication in the journal Cell found that tumors are also home to many types of fungi.

This so-called tumor microbiome is proving so distinct in each type of cancer that some scientists hope to find early signs of hidden tumors by measuring the microbial DNA that spills into the blood. And some research suggests that microbes may make tumors more aggressive or resistant to treatments. If this proves to be the case, it may be possible to fight the cancer by attacking the tumor microbiome along with the tumor itself.

“We need to re-evaluate almost everything we know about cancer through the lens of the tumor microbiome,” said Ravid Straussmann, a Weizmann cancer biologist who collaborated with Dr. Naronsky Haziza on one of the new studies.

Over the past two decades, scientists have drawn a blueprint microbes into the human body by poaching DNA in mouth swabs, skin scrapings, and feces. These surveys have identified thousands of species that live harmlessly in a healthy person, some in total 38 trillion cells. It was believed that many members disinfected It turns out it has its own microbiome.

While researchers have been exploring the healthy microbiome, cancer has mostly remained uncharted territory. No one knows if the millions of cells that make up tumors provide another home for microbes to live in.

In 2017, Dr. Straussmann and colleagues found bacteria living inside pancreatic tumors. They made this discovery while at a loss as to how some tumors could be resistant to chemotherapy drug. It turned out that a type of bacteria that could block the drug was living inside it.

This discovery led Dr. Straussmann and colleagues to perform a large-scale survey of bacteria in more than 1,000 tumors from seven types of cancer. In 2020, they mentioned Find bacteria lurking in all seven species.

At about the same time, a team of researchers at the University of California, San Diego, conducted their own research using a huge database of DNA collected from different types of cancer in the early 2000s.

The goal of the project, called the Cancer Genome Atlas, was to help scientists discover mutations in tumor genes that cause cancer cells to grow uncontrollably. But the San Diego team realized that the initial data might also contain DNA from bacteria in the tumors.

Unfortunately, this meant sifting through the six trillion genetic fragments of the atlas for snippets of bacterial DNA.

“It’s like trying to find needles in a haystack, when there are more haystacks than there are stars in the Milky Way,” said Gregory Sebic-Bor, one of the team.

The research took years, but it paid off. Dr. Sepich-Poore and colleagues found that a small percentage of the DNA fragments in 32 types of cancer belonged to bacteria, not humans.

After researchers published files study In 2020, they teamed up with Dr. Straussmann’s team to see if the tumors also contained fungi.

Fungi are one of the greatest success stories in evolutionary history, with esteem 6.2 million species. They include mushrooms that grow in forests, yeasts that ferment bread and beer, and molds that brought us penicillin.

One of the distinguishing features that all fungi have in common is the way they eat food. They bring up enzymes to break down nearby organic matter and then soak it in. Fungi can also produce a large number of spores, which can survive in all kinds of harsh conditions for years.

We are constantly exposed to fungi, whether by picking up the spores on the skin or eating the food the fungus travels in. Most of them will not reside in our bodies.

“There’s just so much going on,” said Ilian Iliev, an immunologist at Weill Cornell Medicine in New York.

But some species have adapted to live inside us. Skin fungi break down the oils we make. Others feed on the sugars in our mouths and digestive tracts. Scientists have also found other fungi in our bodies whose life is still a mystery. “We really don’t know much,” said Dr. Iliev.

The San Diego and Wiseman researchers looked for fungi in tumors in the same way they searched for bacteria, returning to the galaxy of DNA fragments in the Cancer Genome Atlas. Only this time, they searched for the innate genes. They also examined Dr. Straussmann’s oncology group.

All of the tumors the scientists examined—from 35 different types of cancer—contained fungi, and each type had a distinct mixture of fungal types. mentioned In one study released on Thursday.

In the other new report, Dr. Iliev and colleagues independently have found Fungi in tumors of seven parts of the body: the mouth, esophagus, stomach, colon, rectum, breast and lungs.

Deepak Saxena, a microbial ecologist at New York University who was not involved in either study, was surprised by the sheer scale of the findings. “I wasn’t expecting this much fungus in cancer,” he said. “This will change the way we think.”

Dr. Sepich-Poore and some of his colleagues in San Diego founded a company called Micronoma to turn their research into a blood test for cancer. By looking at the DNA produced by fungi and bacteria in a tumor, they say they can accurately predict what type of cancer the microbes came from.

They don’t know why the test was successful. Geography may be part of the answer: Lung tumors tend to attract microbes that are already in the lung. But some microbes manage to migrate to new organs to reach tumors. It is possible that the specific chemistry within the tumor, such as the level of oxygen, will help determine which microbes will live there.

Both new studies found microbes that appear to be linked to worse outcomes from cancer. For example, Dr. Iliev and colleagues found that people were more likely to die from stomach cancer if their tumors contained a type of fungus called candida tropicalis.

It is possible that some microbes not only settle in tumors, but also help them grow. They may block the tumor from the immune system, inactivate medications or help the tumors spread through the body.

Jessica Galloway-Peña, a microbiologist at Texas A&M University, who was not involved in the new studies, cautioned that this research alone cannot prove whether a microbe has any such effect. Scientists will need to conduct experiments with cancer cells in a dish or on animals.

“Okay, it’s related to a specific type of tumor, but does that just mean it’s largely living with the tumor, or does it actually cause the tumor to increase in size and progression?” asked Dr. Galloway Peña. “You just don’t know at this point.”

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