Immune checkpoint inhibitors (ICIs) are a breakthrough cancer therapy, but only a minority of patients responds to treatment. New research adds evidence to the idea that bacteria living inside tumors can influence how well patients respond to these drugs.

The findings, published in Cell Reports Medicine, suggest that targeting the intratumoral microbiota could become a new strategy to boost cancer immunotherapy.

Scientists have known that both gut and tumor-residing bacteria can influence treatment success, with recent studies suggesting that probiotics or microbiota-based interventions increase ICI effectiveness. However, more research is needed to fully understand these effects.

Researchers led by Junhong Chen at Central South University in Changsha, China, profiled the intratumoral microbiota and its relationship with treatment response in people with cancer who were receiving ICIs.

Microbial ‘modules’

The team collected data from six cancer types, including melanoma, lung, and gastric cancers, and used a computational approach to separate microbial from human genetic material. 

Certain groups of bacteria, such as Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes, dominated the tumor microbiota, but the composition varied by cancer type and even between people with the same type of cancer. In melanoma, the microbial profiles of people who responded to ICIs were different from those of people who didn’t, the researchers found.

By organizing microbes into “modules” based on how they co-occur, the team found that certain modules in melanoma and gastric cancer were associated with better treatment responses and longer survival, while a module in esophageal cancer was linked to poorer outcomes. Within these modules, specific bacterial species—including Burkholderia, Sphingomonas, and Ligilactobacillus—were associated with these effects as well as with key signals linked to antitumor immunity.

Combination therapy

A computational analysis of the data identified three promising bacteria—Burkholderia cepacia, Paenibacillus megaterium, and Corynebacterium kroppenstedtii—that were linked to better treatment responses in melanoma patients.

Experiments in mice then showed that injecting these bacteria into tumors boosted the effectiveness of ICI therapy by stimulating the activity of certain immune cells. The treatment was safe and had no harmful effects on the animals. Similar beneficial effects were seen in mice engineered to have a human-like immune system, confirming that these bacteria can improve ICI therapy by activating antitumor immunity. 

“Our findings highlight the essential role of the intratumoral microbiome in the clinical effectiveness differences of ICIs, suggesting its potential in future ICIs combination therapy,” the authors say.