Gut Microbiota Play Key Role in Cancer Immunotherapy Efficacy

The presence of certain bacteria may enhance response to PD-1 inhibitors in melanoma.

The success of cancer immunotherapy may be dependent on the commensal bacteria living in the intestines, according to research published by Science. Specific strains were observed to increase the response rate to immunotherapy for advanced melanoma.

Although immunotherapy has improved cancer treatment, only 35% of patients with melanoma respond well to treatment, indicating a need for better therapies, according to the study.

The study authors found that the presence of Bifidobacterium longum, Collinsella aerofaciens, and Enterococcus faecium in the intestines was much higher among patients who responded to immunotherapy compared with non-responders.

The researchers noted that the presence of these bacteria in the gut may boost T cell infiltration into the tumor microenvironment. The bacteria were also found to strengthen the ability of T cells to kill cancer cells, according to the authors.

These findings suggest that the link between gut bacteria and the response to PT-1 inhibitors may be a causal relationship, according to the study.

“Specific bacteria clearly contribute to improved anti-tumor immunity in patients,” said study director Thomas Gajewski, MD, PhD. “The gut microbiota has a more profound effect than we previously imagined.”

Previous studies found that the presence of certain gut bacteria was linked to a better response to immunotherapy in mice.

“We knew there were multiple barriers that can decrease the odds that immunotherapy will work,” Dr Gajewski said. “We initially thought the microbiome was a minor component. But in our current study, these bacteria were a very strong predictor of who would respond.”

The current study included 42 human patients receiving treatment for melanoma, of whom 38 were treated with PD-1 inhibitors and 4 were treated with a CTLA4 inhibitor. Patient stool samples were collected prior to treatment to analyze bacteria.

The authors focused on 8 types of bacteria found to be higher among patients who responded to treatment and 2 species that were more common among patients who did not respond.

Patients who had a higher ratio of beneficial bacteria to non-beneficial bacteria were observed to achieve a clinical response, according to the study.

The authors then collected fecal bacteria from 3 human patients who responded to immunotherapy and from 3 patients who did not. The bacteria were then transferred to the intestines of germ-free mice who were subsequently implanted with melanoma cells.

Tumors were observed to shrink only in mice treated with PD-1 inhibitors if they had gut microbiota from patients who responded to the treatment, according to the study.

These findings suggest that gut bacteria play an important role in cancer immunotherapy response.

“Our results strongly suggest that the microbiota is a major factor, a gatekeeper for the immune response against a tumor,” Dr Gajewski said. “Without microbial support, the immune response just never quite gets going.”

The researchers said that future clinical trials should test the efficacy of Bifidobacteria as a method to enhance immunotherapy. They also hope to discover additional gut bacteria that can improve immune response to cancer.

“Our current results open the avenue for integrating commensal microbial composition along with tumor genomes and germline genetics into a multi-parameter model for maximizing the ability to predict which patients are likely to respond to immunotherapies such as anti-PD-1,” the authors concluded.