AUTHOR=Malczewski Agnieszka Beata , Ketheesan Natkunam , Coward Jermaine I. G. , Navarro Severine 

TITLE=Enhancing Checkpoint Inhibitor Therapy in Solid Tissue Cancers: The Role of Diet, the Microbiome & Microbiome-Derived Metabolites

JOURNAL=Frontiers in Immunology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.624434

DOI=10.3389/fimmu.2021.624434

ISSN=1664-3224

ABSTRACT=Host immunity in the treatment of malignancy plays a central role in the advent of checkpoint inhibitor therapy. The mechanisms involved in long lasting remission remain unclear. Animal studies revealed the microbiome greatly influences host immune response, which seems further supported with human studies linking a higher microbial richness and diversity in long-term responders. This review focuses on the role of diet, the microbiome and the microbiome-derived metabolome in enhancing responses to current checkpoint inhibitor therapy in solid tissue cancers. The Western diet has been associated with dysbiosis, inflammation and numerous metabolic disorders. High-fibre and plant based diets seem improving immune function. The mechanisms through which the microbiota may regulate long-term immunotherapy responses have yet to be determined, although bacterial-metabolites including short chain fatty acids (SCFAs) are recognised to have an impact on T cell differentiation, and may affect T effector/regulatory T cell balance. SCFAs were shown to enhance the memory potential of activated CD8 T cells. Many therapeutic approaches including dietary manipulation and faecal transplantation are currently being explored in order to enhance immunotherapy responses. The microbiome-derived metabolome may be one means through which bacterial metabolic products can be monitored from the start of treatment and could be used to identify patients at risk of poor immunotherapy responses. The current review will discuss recent advances and bring together literature from related fields in nutrition, oncology and immunology to discuss possible means of modulating immunity to improve responses to current checkpoint inhibitor therapy.