OSLO, Norway, September 17th, 2024 – Immune checkpoint inhibitors (ICIs) have revolutionized the cancer treatment landscape and have been approved for treating several malignancies in recent years. However, only a subset of cancer patients receiving ICIs respond to treatment. Therefore, identifying predictive biomarkers of ICI response is an active research area in oncology. In this regard, there is compelling evidence that the gut microbiome influences the response of cancer patients to ICIs; however, there is little consensus on the gut microbiome signatures associated with treatment outcomes.

A recent study conducted at the Gustave Roussy Cancer Institute in France and published in Cell analyzed with shotgun metagenomics baseline fecal samples from 245 non-small cell lung cancer (NSCLC) patients. Following an ecosystem-based strategy, the authors constructed TOPOSCORE, a bacterial signature which accurately estimated the likelihood of a cancer patient responding to ICI treatment. This score, based on 83 bacterial species, was validated in additional 254 NSCLC patients and 216 genitourinary cancer patients, showing TOPOSCORE as a robust standalone biomarker in predicting cancer patient response or resistance to ICIs.

In order to transform the shotgun metagenomics-based TOPOSCORE into a clinically actionable tool with short turnaround time the researchers developed a qPCR-based TOPOSCORE using Bio-Me’s Precision Microbiome Profiling (PMP™) platform. PMP™ qPCR assays were used for targeting 21 out of the 83 bacterial species. Relative abundances obtained by shotgun metagenomics for the selected targets exhibited high Spearman correlation coefficients with PMP™, In addition, the qPCR-based TOPOSCORE reliably stratified NSCLC patients based on their response to ICIs, validating the switch from shotgun metagenomics to qPCR.

In summary, this study developed TOPOSCORE, a gut dysbiosis signature that allows for survival risk stratification of patients with different cancer types receiving ICI treatment. Moreover, Bio-Me’s PMP™ platform allowed the translation of the TOPOSCORE into a rapid and reliable test that could be easily used in clinical routine. 

Arne Materna, co-CEO of Bio-Me, comments: These groundbreaking results developed in collaboration with Gustave Roussy, a world leading cancer center in Europe, clearly demonstrate the diagnostic potential of our proprietary platform. PMP™ delivers on accuracy, reproducibility and speed – features that are key for clinical applicability. Bio-Me is very well positioned to take a lead in the development and commercialization of microbiome diagnostics.

Link to the publication:  https://www.cell.com/cell/fulltext/S0092-8674(24)00538-5

Tags: lungcancer, TOPOSCORE, microbiome, PMP