Dual contribution of the gut microbiome to immunotherapy efficacy and toxicity: supportive care implications and...

The efficacy of immune checkpoint inhibitors (immunotherapy) is increasingly recognized to be linked to the composition the gut microbiome. Given the high rates of resistance, interventions targeting the gut microbiome are now being investigated for its ability to improve the efficacy of immunotherapy. In light of recently published data demonstrating a strong correlation between the efficacy and toxicity of immunotherapy, there is a risk that efforts to enhance immunotherapy efficacy may be undermined by increases in immune-related adverse events (IrAEs) This is particularly important for microbial interventions aimed at increasing immunotherapy efficacy, with many microbes implicated in tumour response also linked to IrAEs, especially colitis. IrAEs have a profound impact on patient quality of life, causing physical, psychosocial, and financial distress. Here, we outline strategies at the discovery, translational, and clinical research phases to ensure the impact of augmenting immunotherapy efficacy is approached in a manner that considers adverse implications. Adopting these strategies will ensure that our ongoing efforts to overcome immunotherapy resistance are not impacted by unacceptable toxicity.