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The Gut Microbiome and Immune Modulation in The Treatment of Malignancy

Babu HS, West N, Cripps A, Sanmugarajah J, Mason R

The potential role of the gut microbiomes in the response and toxicity to immune checkpoint inhibitor therapies (ICIs) in advanced malignancies has been a growing area of interest within the field of medical oncology. A number of pre-clinical and clinical trials have identified different microbiome factors that beneficially impact upon ICI outcomes, including specific microorganisms and diversity and suggested that treatment outcomes can be influenced by modification of the gut microbiome, such as through antibiotic administration. There is coexisting evidence the microbiome may also impact on the toxicity profile of ICIs. Currently, the available literature describes associations between the microbiome and ICI outcomes, but the causal link is yet to be established. Additionally, the studies to date pose problems in the inherent heterogeneity that exists between subjects and respective microbiome composition. While promising, murine-humanised models or germ-free mice do not necessarily exhibit comparable immunocompetency or metagenomic function to humans. The faecal microbiome is likely to play a part of the much larger anti-tumour immune response and patient factors that influence this, which must be viewed holistically in the clinical context. Ultimately, this is a promising area, hurtling forward rapidly. Research is equally underway for optimizing methods to administer treatments to alter these microbiomes, whether it be via faecal transplantation, or supplementation with short chain fatty acids directly to the bowel. Learning more about how the constituent parts of the microbiome exert local and systemic immune responses could herald a significant leap forward in how solid tumours are treated with immunotherapy.