A hot topic nowadays is discussions surrounding the microbes in our gut and the numerous health benefits they provide. What isn’t as frequently discussed, however, is how gut microbial composition can impact an individual’s response to cancer treatments.
Considered an important scientific breakthrough, immunotherapy acts to stimulate the body’s immune system to recognize and kill cancer cells. Several types of immunotherapies exist, including immune checkpoint blockade (ICB), adoptive T cell transfers, and cancer vaccines, to name a few. Each of these treatments works differently. ICB, for example, targets checkpoint molecules that act as “brakes” of the immune system, resulting in immune cell activation. Unfortunately, less than 30% of patients benefit from ICB. Why exactly this happens is complex but some of the diverse clinical responses to ICB can be attributed to differences in the gut microbiome.
The gut microbiome is composed of trillions of tiny organisms such as bacteria, fungi, parasites, and viruses and their presence or absence can predict a patient’s response to ICB. Researchers study the fecal composition of patients on ICB to gain key insights into their gut’s bacterial diversity, or lack thereof. For example, the abundance of the bacterial species Akkermansia muciniphila in fecal samples of patients with advanced epithelial tumors was attributed to better responses to a type of ICB treatment. On the other hand, the presence of certain bacteria can also negatively influence immunotherapy responses. Ruminococcus bromii is a bacterium that breaks down complex sugars in the gut and its absence is associated with better outcomes in lung cancer patients.
Patients undergoing cancer treatments are often prescribed antibiotics as they are more susceptible to infections. While helpful in preventing infections, antibiotics can also reduce the number of beneficial gut bacteria, resulting in reduced immunotherapy treatment effectiveness. Cancer patients who had antibiotics administered within 60 days of immunotherapy fared worse than those that weren’t given the antibacterial drugs. Antibiotics are a double-edged sword and clinicians need to be cognizant of both dosage and duration to properly treat patients receiving ICB.
Finally, not unlike other cancer therapies, there are various toxicities associated with immunotherapy. A major side effect of ICB is colitis, or colon inflammation. Here again, the presence of a Gram-negative anaerobe, Bacteroidetes, helped to dampen the risk of developing colitis in patients on ICB.
Even though the gut microbiota modulates responses to immunotherapies, its unknown how they do this. One suggestion is that certain gut microbes promote a strong CD8+T cell response during ICB treatment. In fact, supplementation with probiotics, or “good” bacteria, inhibits tumor growth by stimulating CD8+ T cells. It’s worth pointing out that other research recommends that probiotic supplements should be avoided during immunotherapy. The reason probiotics should not be taken is because they may impact the balance of “good” bacteria and prevent an effective immune response. Such conflicting results demonstrate the complexity of the gut microbiome and its impact on different cancer types, emphasizing the need to further characterize specific interactions.
It’s apparent that gut microbes can alter immunotherapy responses by interacting with drugs directly or by affecting the host’s immune response. Further research will likely explore how the gut microbiome can be safely altered to improve the efficacy of various immunotherapies. In fact, some microbes are already being used in clinical trials to address immunotherapy non-responders or provide long-term treatment for ulcerative colitis patients, who have a higher chance of developing gut-related cancers.
References:
https://www.sitcancer.org/clinician/resources/melanoma/overview
https://doi.org/10.1016/j.trecan.2021.01.010
https://my.clevelandclinic.org/health/diseases/10351-ulcerative-colitis#:~:text=Colitis%20means%20your%20colon%20is,an%20infection%20and%20is%20lifelong.
https://www.sciencedirect.com/topics/medicine-and-dentistry/bacteroidetes#:~:text=Bacteroidetes%20(~50%25%20of%20the,gastric%20acid%20and%20digestive%20enzymes
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308287/#:~:text=There%20are%20many%20reports%20stating,32%2C80%2C81%5D
Ammarah Naseer
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