What’s in Your Gut?

So in the last post, I talked about checkpoint blockade immunotherapy and the results it had on prolonging survival rates for those with brain metastases. In the post, I referenced a protein called PD-1, which is found on T cells and acts as a brake on the immune response. Using immune checkpoint inhibitor drugs releases that brake and allows the immune system to find and kill cancer cells.

But scientists admit that there are a variety of patient outcomes when using this type of immunotherapy. And a recent article in Science may shed some light on why this happens. Researchers from the University of Chicago concluded that the likelihood that “PD-1 blockade” immunotherapy would work might come down to the levels of “good” and “bad” bacteria in your digestive system…

People who responded well to “PD-1 blockade” immunotherapy had high levels of so-called good bacteria, including: Enterococcus faecium, Bifidobacterium longum, and Collinsella aerofaciens. Higher ratio levels of these strains seemed to increase penetration of T cells into cancer tumors. Those who did not respond well to immunotherapy had an “imbalance in gut flora composition, which correlated with impaired immune cell activity.”

How did they come to that conclusion? The researchers identified microbes found in stool samples of 42 people before they underwent immunotherapy. The results showed that the patients who responded to their immunotherapy had higher levels of eight “good” species of bacteria, while those who did not respond to the treatment had higher levels of two “bad” species of bacteria. All participants who had a higher ratio of good to bad bacteria responded to the treatment, and their tumors shrank.

Then, the scientists transferred the patients’ gut bacteria into germ-free mice. Two weeks later, they transplanted melanoma tumors into the mice. The mice who got bacteria from people who responded to the immunotherapy had tumors that grew more slowly than the mice who got more of the bad bacteria.

In addition, the team found that the anti-PD-1 treatment I mentioned in the last post only worked in mice that received gut bacteria from the responding patients.

Prof. Thomas Gajewski, headed up the study and said the link between the specific gut bacteria and the clinical response to the immunotherapy was so strong that it indicates “a causal relationship.” (This is actually a really strong statement. Scientists are usually very careful about saying something is causal, because they’re basically saying a variable is a cause – if not the cause – of an outcome.) He went on to say, “Specific bacteria clearly contribute to improved anti-tumor immunity in patients. The gut microbiota has a more profound effect than we previously imagined.”

The researchers are looking to test whether probiotics might help increase the effectiveness of immunotherapy and are planning a clinical trial using Bifidobacteria, which is found in many commonly available probiotics. It’s crazy to think that the overuse of antibiotics might be a factor in the increase of cancer diagnoses around the world and that probiotics may be a factor in how well you can fight off cancer. I can’t wait to see more research in this avenue.