Predicting response to immunotherapy based on microbiome and metabolites

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