[New research reveals that cancer is rife with bacteria and fungi
— a rich ecosystem that scientists say offers new possibilities for
the detection and even the treatment of cancer]
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WHO KNEW TUMORS HAVE THEIR OWN MICROBIOMES?  
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Carl Zimmer
September 29, 2022
New York Times
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_ New research reveals that cancer is rife with bacteria and fungi
— a rich ecosystem that scientists say offers new possibilities for
the detection and even the treatment of cancer _

A culture of Candida tropicalis, a type of yeast, isolated from
adenocarcinoma-associated mucosa in the lab of Iliyan Iliev, an
immunologist at Weill Cornell Medicine in New York, Credit Jennifer
Conrad and Iliyan Iliev

 

Look up an image of a tumor on Google, and you’ll probably end up
with a brightly colored cluster of cancer cells on a drab background
of healthy tissue. But for Lian Narunsky 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. “It means the cancer
cells are not alone.”

Scientists have long known that our bodies are home to microbes, but
have tended to treat tumors as if they were sterile. In recent years,
however, researchers have laid that notion to rest, demonstrating that
tumors are rife with microbes.

In 2020, several research teams showed that tumors are home to various
blends of bacteria. And on Thursday, two
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Cell found that tumors are also home to many species of fungi.

This so-called tumor microbiome is proving so distinctive in each type
of cancer that some scientists hope to find early signs of hidden
tumors by measuring the microbial DNA they shed into the blood. And
some research hints that microbes may make tumors more aggressive or
resistant to treatments. If that proves to be the case, it may be
possible to fight cancer by attacking a tumor’s 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 Straussman, a
cancer biologist at Weizmann who collaborated with Dr. Narunsky Haziza
on one of the new studies.

Over the past two decades, scientists have charted the microbes
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the human body by fishing for their DNA in mouth swabs, skin scrapings
and stool. These surveys have identified thousands of species that
live harmlessly in a healthy person, totaling some 38 trillion cells
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Many organs once thought to be sterile
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out to have their own microbiomes.While researchers explored the
healthy microbiome, cancer remained mostly terra incognita. No one
knew if the millions of cells that make up tumors provided another
habitat where microbes might live.

In 2017, Dr. Straussman and his colleagues stumbled across bacteria
living inside pancreatic tumors. They made the discovery while
puzzling over how some tumors managed to resist a chemotherapy drug.
It turned out that a species of bacteria that could block the drug was
living inside them.

[Tiny cells on a micrograph look like oblong dots in pink and blue on
a black background.]

Fungal and immune cells in human breast cancer, with the fungal cells
stained in pink and the human cell nuclei in blue. Credit...Deborah
Nejman and Nancy Gavert

That finding led Dr. Straussman and his colleagues to do a large-scale
survey of bacteria in more than 1,000 tumors from seven kinds of
cancer. In 2020, they reported
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bacteria lurking in all seven types.

Around the same time, a team of researchers at the University of
California, San Diego, carried out their own search using a huge
database of DNA gathered from different types of cancer in the early
2000s.

The project, called the Cancer Genome Atlas, was intended to help
scientists find mutations in tumor genes that make cancer cells grow
uncontrollably. But the San Diego team recognized that the raw data
might also contain DNA from bacteria in the tumors.

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

“It’s like trying to find needles in a haystack, when there are
more straws of hay than there are stars in the Milky Way,” said
Gregory Sepich-Poore, a member of the team.

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

After the researchers published their study
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joined forces with Dr. Straussman’s team to see whether the tumors
contained fungi as well.

Fungi are one of the great success stories in the history of
evolution, with an estimated 6.2 million species
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include the mushrooms that grow in forests, the yeasts that ferment
bread and beer, and the mold that brought us penicillin.

Among the hallmarks that all fungi share is the way they eat. They
squirt out enzymes to break down nearby organic material and then soak
it in. Fungi can also produce vast number of spores, which can survive
in all sorts of extreme conditions for years.

We are constantly being exposed to fungi, whether by picking up spores
on our skin or eating food on which fungi are hitchhiking. Most of
them won’t take up residence in our bodies.

“A lot is just passing through,” said Iliyan Iliev, an
immunologist at Weill Cornell Medicine in New York.

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

 

[A swirl of cells in turquoise fill the frame. Some of the swirls are
lined with small black blobs.]

A section of a human lung tumor, in turquoise, with fungi stained in
black. Credit...Lian Narunsky Haziza and Nancy Gavert

The San Diego and Weizmann researchers looked for fungi in tumors in
much the same way they looked for bacteria, diving back into the
galaxy of DNA fragments in the Cancer Genome Atlas. Only this time,
they looked for fungal genes. And they also inspected Dr.
Straussman’s collection of tumors.

All the types of tumors the scientists examined — from 35 different
types of cancer — contained fungi, and each type had a distinctive
combination of fungal species, as they reported
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released on Thursday.

In the other new report, Dr. Iliev and his colleagues
independently found
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seven parts of the body: mouth, esophagus, stomach, colon, rectum,
breasts and lungs.

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

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

They don’t know why the test works. Geography may be part of the
answer: A lung tumor will tend to attract microbes already in the
lung. But some microbes manage to move to new organs to get inside
tumors. It’s possible that the particular chemistry inside a tumor,
such as its level of oxygen, helps determine which microbes will
thrive there.

Both new studies found microbes that appeared to be associated with
worse outcomes from cancer. For example, Dr. Iliev and his colleagues
found that people were more likely to die of stomach cancer if their
tumors contained a species of fungus called Candida tropicalis.

It’s possible that some microbes don’t just take up residence in
tumors but help them grow. They may cloak the tumor from the immune
system, neutralize drugs or help 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 could not establish if a microbe had any such effect. Scientists
will need to conduct experiments on cancer cells in a dish or in
animals.

“OK, it’s associated with a specific tumor type, but does that
just mean that it’s living hunky-dory with the tumor, or is it
actually causing the tumor to get bigger and progress?” Dr.
Galloway-Peña asked. “You just don’t know at this point.”

_Carl Zimmer writes the “Matter”
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fourteen books, including “Life's Edge: The Search For What It Means
To Be Alive.” @carlzimmer
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* Science
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* biology
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* Medicine
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* microbiome
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* cancer
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