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Bacteria and Cancer Immunotherapy: What’s in Your Gut?

Data from human and mice studies suggest that the composition of gut bacteria plays a role in the effectiveness of certain cancer immunotherapy drugs.

Cancer is characterized by uncontrolled growth as a result of impaired cellular control mechanisms. A particular class of drugs known as PD-1 inhibitors work by blocking a vulnerable pathway in T cells which, if left open, can be exploited by cancer cells to inhibit the immune system. Use of these drugs can slow the growth of certain types of cancer for years. However, one of the main challenges associated with this therapy is that only about a quarter of patients respond to treatment.

Previous studies in mice show that alterations in the composition of their gut bacteria can increase their response rates to PD-1 inhibitors. A report published in Science earlier this month highlights more recent developments in this field of study.

Researchers in France examined the implications of this in humans by analyzing data from a total of 249 patients with lung, kidney, and bladder cancer who were undergoing treatment with PD-1 inhibitors. They found that those who had taken antibiotics before or soon after starting cancer immunotherapy treatment were associated with earlier reoccurrences of cancer and shorter life expectancies.

Upon analyzing the gut bacteria of those who responded and didn’t respond to treatment, they found that responders had higher occurrences of Akkermansia muciniphila, a bacterium found in the lining of the gut. They then transplanted fecal samples from patients into germ-free mice and discovered that those receiving samples from responders responded better to PD-1 inhibitors compared to those receiving samples from nonresponders.

Researchers in Texas reported similar outcomes in melanoma patients undergoing treatment with PD-1 inhibitors. Responders had more diverse gut bacteria and more of a specific species of bacterium that, when transplanted into mice, increased their response rates to treatment.

This connection between gut bacteria and cancer immunotherapy is suspected to be related to the ability of certain bacteria to stimulate the release of a signaling molecule known as IL12. This molecule may in turn help bolster T cell activity.

The findings of these studies suggest that a simple way of enhancing response rates to PD-1 inhibitors could be to avoid antibiotics before and during therapy. Researchers hope to further test the connection between gut bacteria and cancer immunotherapy by performing fecal transplants between human patients. A trial for this is projected to start in California in approximately six months.

Written by Agustin Dominguez Iino, BSc

Reference: Kaiser J. Your gut bacteria could determine how you respond to cutting-edge cancer drugs. Science. Published November 9, 2017.



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