Longitudinal gut microbiome changes in immune checkpoint blockade-treated advanced melanoma

• Published in: Nature medicine Vol. 30; no. 3; pp. 785 - 796
• Main Authors: Björk, Johannes R., Bolte, Laura A., Maltez Thomas, Andrew, Lee, Karla A., Rossi, Niccolo, Wind, Thijs T., Smit, Lotte M., Armanini, Federica, Asnicar, Francesco, Blanco-Miguez, Aitor, Board, Ruth, Calbet-Llopart, Neus, Derosa, Lisa, Dhomen, Nathalie, Brooks, Kelly, Harland, Mark, Harries, Mark, Lorigan, Paul, Manghi, Paolo, Marais, Richard, Newton-Bishop, Julia, Nezi, Luigi, Pinto, Federica, Potrony, Miriam, Puig, Susana, Serra-Bellver, Patricio, Shaw, Heather M., Tamburini, Sabrina, Valpione, Sara, Waldron, Levi, Zitvogel, Laurence, Zolfo, Moreno, de Vries, Elisabeth G. E., Nathan, Paul, Fehrmann, Rudolf S. N., Spector, Tim D., Bataille, Véronique, Segata, Nicola, Hospers, Geke A. P., Weersma, Rinse K.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2024; Nature Publishing Group
• Subjects: 631/114/2415; 631/326/2565/2134; 631/67/1813/1634; Adverse events; Antibiotics; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cancer therapies; Clinical trials; Cognition; Combination therapy; Digestive system; Feces; Gastrointestinal Microbiome - genetics; Genomes; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - therapeutic use; Immunotherapy; Infectious Diseases; Inflammatory bowel disease; Intestinal microflora; Kinases; Medicine; Melanoma; Melanoma - drug therapy; Metabolic Diseases; Microbiomes; Microbiota; Microorganisms; Molecular Medicine; Neurosciences; Patients; Survival
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/s41591-024-02803-3

Multiple clinical trials targeting the gut microbiome are being conducted to optimize treatment outcomes for immune checkpoint blockade (ICB). To improve the success of these interventions, understanding gut microbiome changes during ICB is urgently needed. Here through longitudinal microbiome profiling of 175 patients treated with ICB for advanced melanoma, we show that several microbial species-level genome bins (SGBs) and pathways exhibit distinct patterns from baseline in patients achieving progression-free survival (PFS) of 12 months or longer (PFS ≥12) versus patients with PFS shorter than 12 months (PFS <12). Out of 99 SGBs that could discriminate between these two groups, 20 were differentially abundant only at baseline, while 42 were differentially abundant only after treatment initiation. We identify five and four SGBs that had consistently higher abundances in patients with PFS ≥12 and <12 months, respectively. Constructing a log ratio of these SGBs, we find an association with overall survival. Finally, we find different microbial dynamics in different clinical contexts including the type of ICB regimen, development of immune-related adverse events and concomitant medication use. Insights into the longitudinal dynamics of the gut microbiome in association with host factors and treatment regimens will be critical for guiding rational microbiome-targeted therapies aimed at enhancing ICB efficacy. Understanding the dynamics of the gut microbiota over the course of cancer treatment regimens and their associated adverse events can help identify microbial features that associate with response to immune checkpoint blockade.