The microbiome has the potential to identify individuals who may benefit from combination immunotherapy across various cancers, including rare gynecological cancers, biliary tract cancers, and melanoma. A groundbreaking study conducted by researchers from the Wellcome Sanger Institute, the Olivia Newton-John Cancer Research Institute in Australia, and their collaborators has pinpointed specific bacterial strains associated with a positive response to combination immunotherapy. Published in Nature Medicine on March 1st, the study unveils a distinct collection of microorganisms within an individual’s gut bacteria, offering insights into predicting the efficacy of combination immunotherapy—a notoriously challenging aspect of cancer treatment.

Understanding these identified bacterial strains could pave the way for the development of advanced probiotics, termed ‘live biotherapeutic products,’ aimed at modulating the microbiome to support combination immunotherapy from within. Immunotherapy, a treatment leveraging the body’s immune system to combat cancer, exhibits effectiveness in only a subset of recipients across diverse cancer types. Predicting responders becomes crucial to avoiding unnecessary side effects and ensuring patients receive optimal medical benefits.

The study utilized samples from a large Australian clinical trial where combination immunotherapy demonstrated efficacy in 25% of individuals with advanced rare cancers. Focusing on immune checkpoint inhibitors that block PD-1 and CTLA-4 checkpoints, the researchers analyzed stool samples using deep shotgun metagenomic sequencing. The results unveiled previously uncultivated bacterial strains in responders, leading to the identification of a microbiome signature associated with positive treatment outcomes.

Notably, a machine learning model trained on this signature successfully predicted the response to combination immunotherapy across various cancers and geographic locations. However, when applied to patients receiving a single immunotherapy drug targeting only the PD-1 checkpoint, the model failed to identify responders. This emphasizes the specificity of the relationship between gut microbiota and treatment response, urging the tailoring of diagnostic tests or therapeutics to the specific immunotherapy regimen, irrespective of cancer type.

This move towards personalized medicine holds promise for extending cancer treatments to a broader population, aligning individuals with therapies most beneficial to them. Dr. Ashray Gunjur, the study’s first author, underscores the importance of understanding the microbiome at the strain level for a new era of personalized medicine. Dr. Trevor Lawley, the co-senior author, emphasizes how individual microbiomes shape responses to cancer treatment, highlighting the potential clinical impact of identifying those who would benefit the most and informing the design of future clinical trials.

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