Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients
- Science. 2018 Jan 5;359(6371):97-103. doi: 10.1126/science.aan4236.
- 1. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- 2. Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, TX 77030, USA.
- 3. Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- 4. Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- 5. Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- 6. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- 7. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
- 8. Department of Cell, Developmental and Cell Biology, Oregon Health and Sciences University, Portland, OR 97239, USA.
- 9. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- 10. Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- 11. Department of Infectious Diseases, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- 12. Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- 13. Department of Veterinary Medicine and Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- 14. Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- 15. Centre de Recherche de Jouy-en-Josas, Institut National de la Recherche Agronomique, 78352 Jouy-en-Josas, France.
- 16. Centre d'Investigation Clinique Biothérapie, Institut Gustave-Roussy, 94805 Villejuif Cedex, France.
- 17. Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- 18. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- 19. Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- 20. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. [email protected].
Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human Cancer patients. Here we examined the oral and gut microbiome of Melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher Alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of Melanoma patients with immune checkpoint inhibitors.