How Intestinal Bacteria Help Fight Cancer
Immunotherapy, which shows great promise for treating patients with metastatic malignant neoplasms, has dramatically changed therapeutic forecasts in cancer treatment, especially after the discovery of immune checkpoint inhibitors. However, responses to immunotherapy are heterogeneous and often transient. A problematic aspect is that some patients are resistant to such therapy. A new study focuses on improving immunotherapy outcomes by combining this type of treatment with microbial therapy.
Canadian researchers studying cancer immunotherapy at the Snyder Institute, Cumming School of Medicine (CSM) have identified which specific intestinal bacteria contribute to activating the human immune system to fight cancer diseases and how this process is formed. This discovery will provide a new avenue in the development of drugs for cancer immunotherapy and will help address the important question of why immunotherapy is effective in some cases but does not yield 100% results. The results of the Canadian researchers' study were published in Science. They offer hope that the combination of immune therapy with new microbial therapy will help the immune system better recognize and neutralize cancer cells in certain forms of melanoma, colorectal cancer, and bladder cancer.
Essence of the Study
Lead expert and study director Dr. Katherine McCoy and her team focused their efforts on the potential use of the microbiome to improve the outcomes of immunotherapy. One of the most exciting elements of the gut microbiome is that it is inherently modifiable. Less than 10% of the gut microbiome is genetically determined, and potentially modifiable factors can play a key role in defining its profile. Their recent studies demonstrated that the gut microbiota positively influences anti-tumour immunity and enhances the effectiveness of immunotherapy in certain types of cancer. However, the question remained open as to how intestinal bacteria help achieve such results. In the latest study, the researchers were able to advance in solving this question. They demonstrated how specific gut bacteria enhance the ability of T-cells to recognize, attack, and destroy cancer cells.
Stages of the Study
In the first stage, researchers identified the types of bacteria that positively influence the fight against tumour processes in colorectal cancer. In rodent studies, the scientists used these specific bacteria along with immunotherapy. During the study, one group received the isolated bacteria, while the other did not. With the presence of bacteria in the immunotherapeutic preparation, the tumour process decreased; without bacteria, it did not.
It turned out that the bacteria isolated by the researchers produce inosine, which establishes a direct connection with T-cells. This helps the immune system better recognize cancer, consequently increasing effectiveness. In some cases, the researchers recorded 100% destruction of all cancer cells in colorectal cancer.
Next, the researchers confirmed the obtained model in bladder cancer and certain types of melanoma. A total of 3 "beneficial" bacteria capable of improving the performance of immunotherapy were isolated. The research team is now planning the next stage – trials on humans.
“Determining which specific bacteria improve the outcomes of immunotherapy has become a crucial step towards developing new cancer treatment methods that include microbiological agents,” emphasizes Katherine McCoy. “The microbiome is an amazing collection of billions of bacteria living inside and around us. Therefore, it is critically important to utilize the microbiota for developing biomarkers as well as for identifying therapeutic targets that can be applied in cancer immunotherapy, thereby enhancing its effectiveness.”