Bacteria in tumors can promote cancer.chemistry

It turns out that our bodies harbor a myriad of microorganisms, and so do tumors. Over the past five years, researchers have shown that cancer tissue contains entire communities of bacteria and fungi.It now appears that some bacteria may be cancer accomplices. Nature This week, a team led by Susan Bluman at Fred Hutchinson Cancer Center found that in oral and colorectal tumors, Bacteria live inside cancer cells and promote the production of proteins known to suppress immune responsesMicrobial invaders can set off a chain reaction that prevents the immune system from killing cancer cells, and can also help cancer spread to other parts of the body.

The study doesn’t rule out the role of bacteria in cancer entirely, but it’s very suggestive, says Lawrence Zitvogel, a tumor immunologist at the Gustave Roussy Institute. . “This indicates that bacteria in colorectal and oral tumors can actively disrupt immune balance,” she says.

Confirming that microbes can cause tumors to grow and spread could open up new ways to make cancer treatments more effective, for example by killing bacteria with antibiotics. And because each cancer appears to have a unique microbiome, researchers are investigating whether microbes can be used as diagnostic tools to detect cancer early in blood samples. .

Until recently, most cancer researchers believed tumors were sterile, says Ravid Straussman, a cancer researcher at the Weizmann Institute for Science. But about a decade ago, as a postdoc at the Broad Institute, Straussman accidentally discovered that laboratory-grown human pancreatic and colorectal cancer cells became unresponsive to an anticancer drug named gemcitabine. Mycoplasma Bacteria were present in the culture. The bacteria he discovered “Protects” cells by producing an enzyme that breaks down gemcitabine.

Straussman found that gemcitabine could be disabled in mice with colon cancer. Escherichia coli Straining them and treating them with antibiotics restored the drug’s effectiveness. contributed to drug resistance in human cancers. Straussman and his colleagues are now planning clinical trials to test whether antibiotics can improve treatment of pancreatic cancer.

Soon after, Gregory Sepich Poor, a PhD student in microbiome researcher Rob Knight’s lab at the University of California, San Diego (UCSD), was looking for ways to diagnose pancreatic cancer early. He was inspired by his grandmother’s death from cancer, and inspired by his 2017 paper by Straussman, Sepich-Poore sought fragments of genetic material from microbes to help identify human cancers. I began scrutinizing his extensive DNA database, the Cancer Genome Atlas.

In March 2020, he, Knight, and colleagues reported: Microbial RNA and DNA were present in each of the 33 cancers they studied, and each cancer type had a unique microbiome. The team also found these distinct microbial signatures in blood samples from cancer patients. Based on their findings, Sepich-Poore and Knight co-founded San Diego-based Micronoma. Micronoma aims to identify early stage cancers in blood samples, so-called liquid biopsies.

In late 2020, Straussman and his colleagues confirmed that: Many tumors have characteristic populations of microbes They found that most of them exist inside cancer cells and immune cells, not between cancer cells and immune cells.

This paper is a major step forward in this field.

• Ravid Straussman
• Weizmann Institute of Science

Fungi often colonize tumors as well. In a study of 17,000 tumors published in cell In September, UCSD and Weizmann’s group discovered Fungal species present in each of the 35 cancer typesAgain, each cancer type is associated with a different combination of species, helping refine Micronoma’s diagnostic tools. (Straussman is now a member of the company’s Scientific Advisory Board.)

This paper reported another surprising discovery. Certain combinations of fungal species were associated with decreased survival in several types of cancer, most strongly in ovarian and breast cancers. In October, another group reported something similar. cancer cell: Presence of specific bacterial signatures seemed to hasten death in pancreatic cancerPatients without signatures were twice as likely to survive two years after treatment. “This is an eyebrow-raising discovery,” says co-author Martin Brother. He is a cancer microbiome researcher at Rutgers University in Piscataway and serves on Micronoma’s Scientific Advisory Board.

But none of these findings showed how fungi or bacteria could lead to bad outcomes. We address this question by studying 19 tumors resected from colorectal cancer patients. Mapping the microbial distribution showed that the organism colonized only certain areas of the tumor. These infected areas contained high levels of proteins known to suppress her cancer-fighting T-cells and help the cancer grow. Researchers found that T cells clustered on the outside of these areas, but few were found inside. (Instead, this area contained neutrophils, a type of immune cell that fights infection, among other jobs).

Using a technique called single-cell sequencing, researchers found that bacteria preferentially infect cancer epithelial cells that line the inner surface of organs and infect only those cells. Fusobacterium When Treponema Bacteria were dominant and tended to exhibit both immunosuppressive and cancer-promoting properties.

“This paper fills a critical gap by showing that bacteria within cancer cells can alter cell behavior,” said cancer physician and researcher at Trinity Health in New England. George Miller says.

Bullman and her colleagues also co-cultured Fusobacterium Species with colon cancer spheroids (a small model of human cancer) embedded in a matrix containing neutrophils were compared and compared with spheroids without bacteria. In the presence of bacteria, neutrophils tended to migrate toward cancer cells, similar to patient tumor samples. Researchers also observed infected cancer cells breaking up spheroids and migrating. Bullman thinks this could be a sign of metastasis.

Zitvogel says the paper paints a plausible picture of how microbes thwart the body’s defenses against cancer. Still, the spheroid model is “a reductionist approach,” she warns. With a diverse immune cell arsenal and a diverse and highly beneficial microbiome, the human body may have other mechanisms to prevent cancer metastasis.

The study was small and included only two types of cancer, Straussman added. But “Bullman’s study shows how the tumor microbiome should be investigated,” he says. “This paper is a major step forward in this field.”