The Gut Microbiome in Immunotherapy – Lessons Learned from Melanoma and Implications for Gastrointestinal Tumors

bstract Relevance Immune checkpoint blockade has revolutionized the therapeutic landscape in both hematology and oncology. However, as persistent remissions are achieved in only up to 50 % of patients and considerable differences in survival within patient groups, the search for predictive biomarkers, as well as factors that can be modified to improve response rates, remains highly relevant. Critically, persistent remissions are achieved in up to 50 % of patients. As a result, there is an increasing demand for the identification of predictive biomarkers and novel therapeutic targets. Bacterial species of the gastrointestinal microbiome have been suggested to fill in that gap at an early time point. Critically, most studies have initially been conducted in patients suffering from tumor entities outside of the gastrointestinal tract, meaning that insights into the role of the gut microbiome in immunotherapy are mostly available for diseases such as metastatic malignant melanoma. Within this context, this narrative review summarizes four key lessons from immunotherapy research in melanoma and highlights their implications for the still-growing body of evidence on gastrointestinal cancers. Results Lessons learned from immunotherapy in malignant melanoma: 1. Promising bacterial biomarkers that are intended to predict the course of immunotherapy are proposed, but a homogenous body of evidence is missing 2. Antibiotic treatment prior to immunotherapy may compromise the effectiveness of checkpoint blockade 3. H. pylori might modulate the gastrointestinal microbiome. Consequently, the effectiveness of immunotherapies might be affected. But the role of active or past infections remains to be further investigated. 4. Dietary patterns can shape the gastrointestinal microbiome and possibly immunotherapy-related outcomes