Predicting response to immunotherapy based on microbiome and metabolites

Background

Immune checkpoint inhibition (ICI) has revolutionised the treatment of advanced melanoma, producing long-term durable responses in a proportion of patients. However, clinical response is unpredictable and sadly, a majority or patients will not achieve a long-term response. Additionally, toxicity to ICI is highly unpredictable both in terms of time of onset, organ affected and severity. Such immune related adverse events (irAEs) are common with ICIs and can range from mild to severe to life-threatening. Currently, there is no clinically-useful biomarker for clinical response or toxicity. The gut microbiome has been presented as a potential regulator of immune responses and a number of independent research teams from the US and Europe have demonstrated that patients’ responses to ICI are in part due to intestinal microbiota.

However, many important questions remain – the most obvious of these is the question of mechanism, which remains very much unknown. It is also uncertain whether a favourable response can be tied to a single bacterium, or even a specific combination of species. It may be that the diversity of the gut microbiota that is crucial in determining response. The effects of the microbiota on therapy are unlikely to be due to single species and are rather to changes in the ecology and metabolism of the gut microbiota that together affect cancer immunity

For more information on the study, visit NCT03643289 at clinicaltrials.gov

Goals

Seerave Foundation is supporting two independent centers performing complementary prospective clinical studies:

University Medical Center Groningen (UMCG), Netherlands, under the supervision of Prof. Geke Hospers and Prof. Rinse Weersma. A Seerave Fellow at UMCG will coordinate the efforts undertaken.
King’s College London (KCL), United Kingdom, under the supervision of Prof. Tim Spector and Dr. Veronique Bataille. KCL will lead a consortium of UK Melanoma Centres

Both studies aim at performing longitudinal analysis of the nutritional status and the composition and function of the gut microbiome in melanoma patients undergoing immunotherapy. The ultimate goal is to integrate the collected data into predictive “–omics signatures” including other biomarkers from blood and tumors, host genetics and immunomics as well as other clinical parameters.