Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome 2024 Derosa et al

Highlights

• Two topological metagenomic bacterial communities are associated with patient survival
• A unidimensional dysbiosis score was calculated, allowing survival risk stratification
• Gut dysbiosis TOPOSCORE computed from lung cancers could be applied to other cancers
• The metagenomics-based score was translated into a rapid 21-bacteria-based qPCR test

Summary

The gut microbiota influences the clinical responses of cancer patients to immunecheckpoint inhibitors (ICIs). However, there is no consensus definition of detrimental dysbiosis. Based on metagenomics (MG) sequencing of 245 non-small cell lung cancer (NSCLC) patient feces, we constructed species-level co-abundance networks that were clustered into species-interacting groups (SIGs) correlating with overall survival. Thirty-seven and forty-five MG species (MGSs) were associated with resistance (SIG1) and response (SIG2) to ICIs, respectively. When combined with the quantification of Akkermansia species, this procedure allowed a person-based calculation of a topological score (TOPOSCORE) that was validated in an additional 254 NSCLC patients and in 216 genitourinary cancer patients. Finally, this TOPOSCORE was translated into a 21-bacterial probe set-based qPCR scoring that was validated in a prospective cohort of NSCLC patients as well as in colorectal and melanoma patients. This approach could represent a dynamic diagnosis tool for intestinal dysbiosis to guide personalized microbiota-centered interventions.

Open access, https://www.cell.com/cell/fulltext/S0092-8674(24)00538-5

 

Gut microbiome discovery provides roadmap for life-saving cancer therapies

"Despite their small size, gut bacteria wield large influence over the effectiveness of certain cancer drugs. Researchers have now found that the ratio of specific microbial communities in the gut can help to predict who will respond to next-generation drugs for treating some kinds of cancer1.

The findings will also help to identify healthy volunteers who could donate faecal bacteria to transfer into the intestines of people who do not respond to these drugs, a procedure known as faecal microbiome transplantation, study co-author Laurence Zitvogel, an immunologist and oncologist at the Gustave Roussy Cancer Campus in Villejuif, France, wrote in an e-mail to Nature.

The work “is a breakthrough from a diagnostic point of view”, says Fabio Grassi, an immunologist at the Institute for Research in Biomedicine in Bellinzona, Switzerland. The findings, he says, also highlight how the delicate balance of gut microbial species can affect the success of high-stakes therapies, such as immune checkpoint inhibitors. This treatment helps the immune system to recognize and attack cancer cells and is the focus of the new research. The findings were published today in Cell."

https://www.nature.com/articles/d41586-024-02070-9