Intestinal bacteria increase the effectiveness of cancer treatment

Researchers have discovered a strain of intestinal bacteria that enhances the effect of immune checkpoint inhibitors, a type of cancer therapy. This bacterium stimulates the activity of dendritic cells, which in turn direct and concentrate immune T cells against tumors. This discovery helps explain differences in patient response to treatment and paves the way for new therapeutic strategies based on modulation of the intestinal microbiota.

In recent years, treatments that activate the immune system have become a promising direction in the fight against cancer. In particular, immune checkpoint inhibitors — monoclonal antibodies designed to enhance the response of T lymphocytes — have achieved long-term remission in some patients with advanced forms of cancer. However, despite proven effectiveness in a number of cases, treatment outcomes vary from patient to patient. Scientists attribute this heterogeneity, among other things, to the composition of the gut microbiota, whose role in regulating the systemic immune response is becoming increasingly apparent.

Previous studies have already shown the influence of microbiota on the activation of immunity during chemotherapy. Other studies have demonstrated that the presence of certain bacteria can increase the effectiveness of checkpoint inhibitor therapy, for example, by stimulating macrophages, monocytes, or directly affecting T cells in experiments on mice.

“Current research indicates that the microbiome is involved in the metabolism, absorption, and even the mechanism of action of anticancer drugs, whether chemotherapy or immunotherapy,” explains Peter Turnbull, professor of microbiology and immunology. “Although much of the data has been obtained in preclinical models, consistent correlations are also beginning to emerge in human patients,” he adds.

Until now, the exact types of bacteria responsible for this effect remained unknown. However, a significant breakthrough was recently published in the journal Nature by a group of scientists from the National Cancer Center in Tokyo. They were able to identify a specific strain, Hominenteromicrobium mulieris (YB328), belonging to the Ruminococcaceae family. This bacterium was found in significantly higher quantities in stool samples from patients who responded positively to PD-1 blocker therapy.

The PD-1 protein, expressed on the surface of T cells, plays a key role in suppressing the immune response: its binding to PD-L1 or PD-L2 ligands inhibits the activity of T lymphocytes, which cancer cells exploit to evade immune surveillance.

To study the effect of microbiota on treatment efficacy, Japanese researchers analyzed stool samples from 50 patients receiving checkpoint inhibitor therapy and performed fecal microbiota transplantation in mice with tumors. As a result, rodents that received microbiota from patients who responded positively to treatment also showed improvement. In contrast, mice that received microbiota from non-responsive patients were resistant to therapy.

After more than a year of in-depth analysis, the scientists identified the YB328 strain as the key factor in this difference. It turned out that this bacterium activates CD103+CD11b– dendritic cells, which are critical for triggering an effective cytotoxic response. These cells migrate to tumors via the bloodstream, where they activate CD8+ T cells capable of destroying cancer cells.

“Mice demonstrated increased antitumor efficacy of PD-1 blockade in the treatment of non-responding patients with fecal transplants supplemented with YB328,” the study authors note. “This result suggests that YB328 may play a dominant role in this immune modulation,” they add.

This discovery confirms the hypothesis of a direct link between the composition of the gut microbiota and the effectiveness of cancer immunotherapy. In the future, this could lead to the development of new adjuvant strategies involving the use of specific probiotics, special diets, or even fecal microbiota transplantation. In the near future, researchers plan to begin clinical trials to test whether the results obtained in animals can be transferred to humans.