Microbiome helps identify those who benefit from combination immunotherapy

A new study by researchers at the Wellcome Sanger Institute, Australia's Olivia Newton-John Cancer Research Institute, and collaborators is the largest study of its kind, identifying specific findings associated with positive responses to combination immunotherapy. identified bacterial strains.

This study natural medicine In an article titled “Gut microbial signature combined with immune checkpoint inhibition across different cancer types” details the collection of characteristic microorganisms contained in an individual's gut microbiome. This will help identify who will benefit from combination immunotherapy and help explain why the effectiveness of this treatment is otherwise difficult to predict.

“Immune checkpoint blockade (ICB) targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte protein 4 (CTLA-4) has shown significant but unpredictable responses across a variety of cancers. ,” the researchers wrote. “Studies suggest that there is a relationship between the composition of the gut microbiota in cancer patients and their clinical response to ICB. However, it is important to define microbiome-based biomarkers that generalize across cohorts. That was difficult.”

Immunotherapy is highly effective, but only works for some patients across a wide range of cancers. Being able to predict who is most likely to respond to treatment can help ensure that patients tolerate these unnecessary side effects without gaining any medical benefit.

The study used samples collected in a large multi-centre clinical trial in Australia that covered a wide range of cancers, including rare gynecological cancers, neuroendocrine tumors, upper gastrointestinal tract cancers and bile duct cancers. Combination immunotherapy was effective in 25% of patients with advanced rare cancers. .

This clinical trial focused on checkpoint inhibitors. These cancer drugs block the body's immune checkpoint proteins, allowing immune cells to destroy cancer cells. In this case, immunotherapy blocked the PD-1 and CTLA-4 checkpoints.

Using stool samples from clinical trial patients, the researchers performed deep shotgun metagenomic sequencing to map all the microorganisms in participants' microbiomes down to the strain level.

They discovered multiple bacterial strains in patients who responded well to treatment, many of which had not been previously cultured. This allowed them to identify microbiome characteristics found in patients who responded well to treatment.

The researchers conducted a meta-analysis of previous studies and applied their signatures across different cancers, such as melanoma, and across countries to identify patients with cancers more likely to respond to combination immunotherapy. We discovered that we can predict which individuals will be present.

However, when the machine learning model was applied to patients who received only one immunotherapy drug that targets only the immune checkpoint receptor PD-1, it failed to identify patients who would respond to treatment.

This suggests that the relationship between gut microbiota and treatment response is specific to certain treatment combinations.

Lead author Dr Ashley Ganger from the Wellcome Sanger Institute and the Olivia Newton John Cancer Research Institute in Australia said: Level of personalized medicine. Having this extra resolution is critical to understanding what's going on inside the human body and the interactions between cancer treatments and the microbiome. Being able to test the specific mechanisms of the relationship between specific bacterial strains and responses is the next area of ​​this research, which could benefit human health in a variety of ways. ”