Common bacteria may help some viruses that cause cancer by suppressing the Immune system

Gut bacteria have a profound impact on health by aiding digestion, providing nutrients and metabolites, and working with the immune system to fend off pathogens. Some gut bacteria, however, have been implicated in progression of cancers of the gut and associated organs.

A new study by researchers from the University of Chicago 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 the virus and commensal bacteria are present in mice, three genes known as negative immune regulators are expressed more, or upregulated, which in turn tamps down the immune response that would otherwise kill the tumor cells. Two of these three negative immune regulators are also known to be indicators of poor prognosis for humans with some forms of cancer.

Some cancer-causing retroviruses take advantage of gut microbes to spread and replicate. For example, in a 2011 study, Golovkina and her team found that a virus that causes mammary tumors in mice depends on gut bacteria, enabling the virus to block the immune responses from recognizing and eliminating infected cells. Thus, the microbes help the virus replicate and as a result, tumors develop.

In the new study, the researchers wanted to see if commensal bacteria affected the development of a virus-induced cancer in another way besides assisting its replication. The team performed a series of experiments with immunodeficient mice that were specially engineered, so they lacked the adaptive immune system. In the germ-free setting, these mice developed tumors when exposed to the virus with the same frequency as immunosufficient SPF mice with intact immune systems. So, the anti-tumor immune response was being counteracted by microorganisms, which were subsequently identified as commensal bacteria.

The researchers then found that commensal bacteria induced three genes known as negative immune regulators in infected mice. These genes normally act to shut down the immune system after it dealt with a pathogen, but in this case, they held back an immune response directed against cancer cells. Two of the three upregulated negative immune regulators—Serpinb9b and Rnf128—are also known to be indicators of poor prognosis for humans with some spontaneous cancers.

Reference:

Tatyana Golovkina et al,Gut commensal bacteria enhance pathogenesis of a tumorigenic murine retrovirus,Cell Reports,DOI:10.1016/j.celrep.2022.111341