A recent study has discovered that a type of gut bacteria can strengthen the immune system and improve cancer immunotherapy to combat sarcoma tumors in mice. Immunotherapy, which uses the body’s immune system to fight cancer, has been successful in treating lung cancer and melanoma in some patients. Researchers are now looking into ways to enhance immunotherapy for cancers that have not responded well to the treatment, in the hopes of helping more patients.Researchers at Washington University School of Medicine in St. Louis discovered that a specific strain of gut bacteria called Ruminococcus gnavus can improve the effectiveness of cancer immunotherapy in mice. The study, published on May 17 in Science Immunology, indicates a potential new approach for using gut microbes to enhance the cancer-fighting capabilities of immunotherapy.
According to the senior author of the study, Marco Colonna, MD, the Robert Rock Belliveau, MD, Professor of Pathology, “The microbiome plays a crucial role in activating the body’s immune system to target cancer cells.” This research highlights the significance of a particular bacterial species in assisting the immune system’s response to cancer.
Researchers have discovered that a certain type of bacteria in the intestines can enhance the effectiveness of an immunotherapy drug in eliminating tumors in mice. This finding is a significant advancement towards developing probiotics that can improve the ability of immunotherapy drugs to treat cancer.
Cancer immunotherapy works by using the body’s immune cells to target and destroy tumors. One method involves using immune checkpoint inhibitor drugs to activate the immune system by removing the natural restraints that keep immune T cells in check, preventing them from causing harm to the body. However, some tumors can counteract this by suppressing the immune cells, reducing the effectiveness of the inhibitors.The authors, Colonna and Molgora, along with colleague Schreiber, successfully eliminated sarcoma tumors in mice by using a two-pronged inhibition approach. By inhibiting the protein TREM2, which is produced by tumor macrophages to prevent T cells from attacking the tumor, they were able to demonstrate that a cancer immunotherapy drug was more effective when TREM2 was blocked. This suggests that TREM2 can reduce the effectiveness of immunotherapy. This groundbreaking experiment formed the basis of their collaboration.The researchers of the new study made an unexpected discovery. They found that TREM2 mice had a similar positive response to the checkpoint inhibitor even when they were housed with mice that did not have the protein. This finding occurred when the researchers went against their usual protocol of separating the mice before treating them with the inhibitor.
When mice live together, they share microbes. The researchers suspected that the effects might be due to exchanges of gut bacteria. They collaborated with Jeffrey I. Gordon, MD, the Dr. Robert J. Glaser Distinguished University Professor, and co-first author Blanda Di Luccia, PhD, a postdoctorala study on the intestinal microbes of mice treated with immunotherapy. They discovered that there was an increase in the presence of Ruminococcus gnavus in the successful treatment group, while the mice that did not respond to the therapy lacked this microbe. Colonna also mentioned that R. gnavus has been identified in the gut microbiota of cancer patients who have positively responded to immunotherapy. Fecal transplants from these patients have also shown to benefit unresponsive patients in clinical trials. Khantakova, a graduate student and co-first author of the study, was also involved in the research.R. gnavus was given to the mice and then their tumors were treated with a checkpoint inhibitor. The tumors decreased in size, even when TREM2 was present to weaken the effect of the immunotherapy. Dr. Gordon, who is the director of the Edison Family Center for Genome Sciences & Systems Biology, pointed out that there is increasing evidence that the microbiota enhances immunotherapy. He mentioned that identifying specific species, such as R. gnavus, could result in a new probiotic that could work together with immunotherapy to improve cancer treatment. The researchers’ next goal is to figure out how R. gnavus helps in rejecting tumors, which could uncover new insights into the potential benefits of this bacteria.New methods are being discovered to assist cancer patients, such as the potential use of immune-activating metabolites produced by microbes in the body. This knowledge may lead to the use of metabolites as enhancers for immunotherapy. Additionally, microbes can escape from the gut and stimulate an immune response in tumors, or activate gut T cells that can travel to the tumor to launch an attack. The researchers are investigating these three possibilities.
