Does the Microbiome Help the Body Fight Cancer?

Source: The Scientist, August 2019

A few years ago, biologist Ze’ev Ronai discovered that the mouse strain he’d been working with for the last decade was particularly resistant to melanoma. He’d been studying the mice—which lack a functional copy of the protein-regulating enzyme RNF5—with colleagues at Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California, to learn more about the cellular stress response pathways of which RNF5 is a part. When, during research on those stress pathways’ involvement in cancer progression, the scientists inoculated the RNF5 knockouts with melanoma cells, they were surprised to find that tumors grew more slowly, and the mice showed heightened antitumor immune responses compared with wildtype animals.

Excited by the implications for immunotherapy research, Ronai’s group planned to demonstrate that the knockout mice’s immune cells, which are produced by bone marrow, were sufficient to elicit the same cancer-resistant phenotype when transferred into wildtype animals. But the experiment didn’t work—a bone marrow transfer didn’t slow tumor growth. “To us,” Ronai says, “this indicated that there was something else beyond the immune system component that elicited the phenotype.”

Scouring the melanoma literature for inspiration, the team came across a 2015 study by the University of Chicago’s Thomas Gajewski and colleagues. That research showed that mice with melanoma responded better to immunotherapy treatment—specifically, to anti-PD-L1 immune checkpoint therapy, which works by enhancing antitumor responses—if their guts contained high concentrations of a bacterial genus called Bifidobacterium. It piqued Ronai’s interest, and “led us to examine whether the differences we saw here could be linked to the microbiota,” he says.