Some cancer-causing viruses suppress the immune system with the help of common bacteria

A new study by University of Chicago researchers shows that some commensal bacteria promote the development of leukemia caused by the murine leukemia virus (MuLV) by suppressing the animal’s adaptive anti-tumor immune response. . When both viruses and commensal bacteria are present in mice, three genes known as negative immune regulators are more expressed or upregulated, suppressing immune responses that otherwise kill tumor cells. Two of these three negative immune regulators are known to be indicators of poor prognosis in humans with certain types of cancer.

“These two negative immune regulators are very well documented as poor prognostic factors in some human cancers, but no one knew why,” says Chicago. said Tatyana Golovkina, PhD, professor of microbiology at the university and lead author of the study. “Using mouse models of leukemia, we found that bacteria contribute to the upregulation of these negative immune regulators, allowing developing tumors to escape recognition by the immune system.”

The results of the study “Gut commensal bacteria enhance virulence of tumorigenic murine retroviruses” were published on September 13. cell report.

Cancer is usually thought to be the result of spontaneous mutations that cause cells to grow and proliferate uncontrollably, forming tumors. In 1910, a pathologist named Peyton Routh took samples from chicken cancerous tumors and injected them into healthy birds, who also developed cancer. However, researchers later discovered that cancer was transmitted by retroviruses. rice field.

Some cancer-causing retroviruses use intestinal microbes to spread and replicate. For example, in a 2011 study, Golovkina and her team found that the virus that causes mammary tumors in mice depends on gut bacteria. This allows the virus to block the immune response that recognizes and eliminates infected cells. Microorganisms thus help the virus to replicate, resulting in tumors.

In the new study, researchers wanted to see if commensal bacteria influence the development of virus-induced cancer in other ways besides helping them replicate. Because GF) mice were used, microbial-free and specific pathogen-free (SPF) mice do not have pathogenic microbes that can cause disease, but have common commensal microbes. Contains bacteria that normally live in the gut. Both GF and SPF mice were infected with murine leukemia virus (MuLV). Although the virus infected and replicated equally in both types of mice, only SPF mice developed a high frequency of tumors.

All virus-induced cancer cells express viral antigens, or molecules that mark them as foreign to the host and target them for immune attack. Because virus-induced tumor cells must be protected from immune system attack in order to continue replicating, Golovkina’s team enables virus-induced cancer cells to survive within the host. We searched for microbe-dependent immune evasion mechanisms.

The team performed a series of experiments in specially engineered immunodeficient mice that lacked an adaptive immune system. In a sterile environment, these mice developed tumors with the same frequency as immune-sufficient SPF mice with intact immune systems when exposed to the virus. As such, anti-tumor immune responses were counteracted by microbes later identified as commensal bacteria.

The researchers then found that the commensal bacteria induced three genes known as negative immune regulators in infected mice. These genes normally act to shut down the immune system after dealing with pathogens, but in this case they suppressed the immune response against cancer cells. 2 of 3 upregulated negative immune regulators — Serpinb9b When Rnf128 — It is also known to be an indicator of poor prognosis in humans with some spontaneous cancers. Not all commensal bacteria have tumor-promoting properties, so Golovkina and her team continue to explore why this immunosuppressive ability is only exerted when both virus and bacteria are present. I’m here.

“Now we have to understand what is special about bacteria with these properties.

The study, “Gut Commensal Bacteria Enhance Pathogenesis of Tumorigenic Murine Retroviruses,” was supported by the National Institutes of Health and the National Center for Diabetes and Gastroenterology and Kidney Disease Gastroenterology Research Core Center. Other authors include her Jessica Spring, Aly A. Khan, Sophie Lara, Kelly O’Grady, Jessica Wilks, Sandeep Gurbuxani, Steven Erickson, and Alexander Chervonsky from the University of Chicago. Michael Fischbach and Amy Jacobson at Stanford University.

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material provided by University of ChicagoOriginal by Matt Wood. Note: Content may be edited for style and length.