A growing emphasis on precision medicine makes furthered knowledge and understanding of the microbiome’s influence on immune responses and cancer imperative. The discovery of strategies for manipulating the microbiome, to thereby augment therapeutic responses, relies on understanding the specific factors that influence gut microbiome mechanisms. Although several species of intestinal bacteria have already been linked to the enhanced efficacy of immunotherapies, exactly how the microbiome is able to enhance anti-tumor immunity remains in question.
Gut Bacteria and Immunotherapy
The latest clinical research further suggests the role of the microbiome and elucidates the mechanisms of action underlying its impact on certain types of cancer treatments. In a recent study, researchers at the Snyder Institute for Chronic Diseases at the Cumming School of Medicine (CSM) investigated how gut bacteria help the immune system attack cancerous tumors and how they accomplish this, providing an updated understanding of immunotherapy and its differing outcomes.
Led by Kathy McCoy, Ph.D., director of the International Microbiome Center at the University of Calgary, the team of researchers first identified bacterial species associated with colorectal cancer treated with immunotherapy. They then introduced these bacteria into germ-free mice with immune checkpoint blockage – cancer immunotherapy – and conducted their investigation.
Benefits of Certain Bacterial Strains
Researchers found that three bacterial species – Bifidobacterium pseudolongum, Lactobacillus johnsonii and Olsenella – significantly enhanced the efficacy of immune blockades. These specific bacteria were essential to immunotherapy success, drastically shrinking tumors, as evidenced by participants who did not receive beneficial bacteria for whom immunotherapy had no effect.
The study’s authors also reported that intestinal B. pseudolongum modulated an enhanced immunotherapy response through the production of the metabolite inosine. “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,” according to Dr. Lukas Mager, MD, Ph.D., senior postdoctoral researcher in the McCoy lab and first author of the study.
In addition, the team validated their findings in both bladder cancer and melanoma cases, in which the beneficial bacteria species associated with tumors in mice were also found in cancers in humans.
“Collectively, our study identifies a novel microbial metabolite-immune pathway that is activated by immunotherapy that may be exploited to develop microbial-based adjuvant therapies,” the researchers wrote.
The latest findings were published in Science and reveal that combining immunotherapy with specific microbial therapy can help the immune system recognize and attack cancer cells in three forms of cancer – melanoma, bladder, and colorectal cancers. However, further study is needed to validate these results in human trials.
Building on prior studies that provided strong evidence of the positive effects of anti-tumor immunity and gut microbiota, the recent study elucidates how certain bacteria are able to enhance the function of T-cells, that are ultimately responsible for attacking and destroying cancerous cells. This new knowledge is essential to the development of anti-cancer therapies; identifying how microbes may improve immunotherapy is crucial to designing more effective therapies which may include microbials. Further research is needed to expand the current understanding and shed light on how this knowledge can be used to improve the efficacy and safety of anti-cancer therapy, improve cancer patient survival rates, and enhance patient wellbeing.
