How Gut Health Affects Bladder Cancer and Immunotherapy

T-cells are having their moment. Our immunity system’s foot soldiers, they were often the forgotten warriors in the battle against COVID-19. For while antibodies earned the headlines, T-cells are why children can successfully ward off attacks from an unfamiliar virus. They may even offer longer-lasting protection following vaccination than antibodies. Plus, while immunotherapy can boost a body’s ability to battle disease, it’s had a mixed track record when it comes to bladder cancer. Now research suggests that microbes in our guts can supercharge immunotherapy treatments. Plus, keeping a healthy gut can reduce your chances for getting the disease. Here’s what to know. 

Late-stage Bladder Cancer Risks

The result of genetic mutations, cancer occurs when damaged cells continue to divide and spread, rather than die off. These cells can form tumors which in some cases can be life threatening. When cancerous cells attack the balloon-shaped bladder, it can be particularly deadly. In the United States, some 56,000 men and 17,500 women are diagnosed with the disease each year. Around 17,000 die from it. Worldwide, it’s the tenth most common cancer with over half-a-million new cases each year.

Most patients with bladder cancer have transitional cell carcinoma which can form in the bladder’s inner tissue. Other versions include squamous cell carcinoma and small cell carcinoma. Like other cancers, treatment depends upon how far the disease has progressed (also called stages.) With nonmuscle-invasive bladder cancer, for example, the disease hasn’t yet reached the bladder’s layer of muscle but remains in its lining. Usually this tumor can be scraped away from the bladder wall. With more advanced stages, radiation or chemotherapy may also be used. Although generally survivable when detected early, once it has spread to other parts of the body, its five-year-survival rate is just over five percent. 

Many patients with the worst prognosis have a genetic mutation––their FGFR3 gene is overactive. They also have fewer T-cells than other patients with cancer who don’t have the mutation. In the past, immunotherapy, especially immune checkpoint blockade drugs, haven’t reduced tumors in patients with the FGFR3 gene. For most, chemo was the only option. A recent study suggests that some of them may respond to drugs, particularly in concert with erdafitinib (Balversa), which was approved by the FDA in 2019 to specifically target the gene. As study author William Y. Kim, MD,  from the University of North Carolina Lineberger Comprehensive Cancer Center explains, “Despite prior work suggesting that FGFR3-mutation bladder cancers should not be treated with immunotherapy, our study demonstrates the opposite, so we believe that immunotherapy should be offered without hesitation.”

Our Gut Health and Cancer

Yet immunotherapy may not need a drug to increase its effectiveness but rather a naturally occurring bacteria. A community of microorganisms like bacteria or fungi is called a “microbiome.” In our bodies, there are unique microbiomes in places like the mouth, the skin, and the vagina. However, most microbes are found in the gut. Outnumbering human cells ten to one, these microbes can form a microbiome that weighs ten pounds. They assist our bodies in digestion and our immune response. While the existence of the microbiome in our guts was only widely acknowledged in the past quarter-century or so, new research reveals how vital the health of these bacteria is.

That’s because the microbiome in our gut must be in balance. This collection of good and bad bacteria has an outsized impact on our health. It’s not just about tummy trouble. Imbalances weaken your immune system while increasing inflammation. Not only will this make you more susceptible to illnesses––including COVID-19––but it can also heighten your risk of developing cancer. As Margie L. Clapper, PhD, deputy scientific director at Fox Chase Cancer Center explains, “The inner surface of the colon is covered in a mucus layer. If bacteria have an opportunity to invade that and get close to tissue, if that defense is missing, it can start an inflammatory reaction, which has the potential to encourage tumor growth.” Worse, tumors can actually carry information about the gut’s microbiome to other locations––meaning imbalances can affect a wide range of cancers.

When it comes to bladder cancer, imbalances in gut bacteria not only affect outcomes but may impact the effectiveness of immunotherapy. At the Snyder Institute for Chronic Diseases at the Cumming School of Medicine (CSM), researchers have not only explored the role of the gut’s microbiome in fighting cancer but have discovered which gut bacteria help our immune system battle the disease. While immunotherapy hasn’t always been successful in fighting cancer, a new study from the Snyder Institute suggests that when combined with specific bacteria the results are much more promising.

Building on research showing how specific bacteria embolden T-cells, researchers identified and introduced bacterial species during immunotherapy. When germ-free mice received those bacteria in combination with the immune checkpoint blockade, results were clear cut. Tumors shrank. Immunotherapy failed with the mice who didn’t get the bacteria.

“We found that these bacteria produce a small molecule, called inosine,” explained study author, Dr. Lukas Mager, MD, PhD. “Inosine interacts directly with T-cells and together with immunotherapy, it improves the effectiveness of that treatment, in some cases destroying all the colorectal cancer cells.”

That treatment was later shown to be equally effective with melanoma and bladder cancer. For anyone or their loved ones battling bladder cancer, the news offers a ray of hope. Yet maintaining gut health is vitally important for everyone. Increasingly, studies have shown that genetics generally plays a smaller role in our cancer risk than the choices we make. Making a decision to eat more fruits and vegetables along with fiber and foods loaded with beneficial bacteria like yogurt can help you live a healthier, happier life.

References

• Bladder cancer
• GLOBOCAN 2020: Bladder cancer 10th most commonly diagnosed worldwide
• Advanced bladder cancers respond to immunotherapy regardless of gene mutation status
• Having Healthy Gut Bacteria Is Important for Overall Health and Cancer Prevention
• Researchers discover the microbiome’s role in attacking cancerous tumors
• Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy