Gut bacteria strengthen the immune system to fight tumour, study finds

Immunotherapy, which uses the immune system to fight cancer, benefits about one in five cancer patients, showing significant success in lung cancer and melanoma. Researchers are now working to enhance immunotherapy for cancers, aiming to help more patients.

Now, researchers at Washington University School of Medicine in St. Louis have found, in mice, that a strain of gut bacteria – Ruminococcus gnavus – can enhance the effects of cancer immunotherapy. The study, published in the journal Science Immunology, suggested a new strategy of using gut microbes to help unlock immunotherapy’s untapped cancer-fighting potential.

Cancer immunotherapy employs the body’s immune cells to target and destroy tumors. One such treatment uses immune checkpoint inhibitor drugs to unleash the immune system by releasing the natural brakes that keep immune T cells quiet, a feature that prevents the body from harming itself. However, some tumors fight back to suppress the attacking immune cells, dampening the effectiveness of such inhibitors.

In the study, researchers eliminated sarcoma tumors in mice by inhibiting TREM2, a protein made by tumor macrophages that prevents T cells from attacking the tumor. Blocking the gene made cancer immunotherapy more effective, indicating TREM2 reduces immunotherapy's efficacy. Notably, TREM2 mice housed with TREM2-deficient mice showed the same beneficial response to the checkpoint inhibitor, revealing unexpected environmental effects on treatment outcomes.

Additionally, the researchers studied the microbes in the intestines of the mice that were treated successfully with immunotherapy and found an expansion of Ruminococcus gnavus, compared with a lack of such microbes in mice that didn’t respond to the therapy.

“The microbiome plays an important role in mobilizing the body’s immune system to attack cancer cells. Our findings shine a light on one bacterial species in the intestine that helps an immunotherapy drug eliminate tumors in mice. Identifying such microbial partners is an important step in developing probiotics to help improve the effectiveness of immunotherapy drugs and benefit more cancer patients,” explained the study’s senior author, Marco Colonna, Professor of Pathology.

Reference: Blanda Di Luccia et al. ,TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti–PD-1 tumor immunotherapy. Science Immunology.(2024) .DOI:10.1126/sciimmunol.adi5374