Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Academic Article uri icon


  • 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.

published proceedings

  • Science

altmetric score

  • 1035.632

author list (cited authors)

  • Gopalakrishnan, V., Spencer, C. N., Nezi, L., Reuben, A., Andrews, M. C., Karpinets, T. V., ... Wargo, J. A.

citation count

  • 2192

complete list of authors

  • Gopalakrishnan, V||Spencer, CN||Nezi, L||Reuben, A||Andrews, MC||Karpinets, TV||Prieto, PA||Vicente, D||Hoffman, K||Wei, SC||Cogdill, AP||Zhao, L||Hudgens, CW||Hutchinson, DS||Manzo, T||Petaccia de Macedo, M||Cotechini, T||Kumar, T||Chen, WS||Reddy, SM||Szczepaniak Sloane, R||Galloway-Pena, J||Jiang, H||Chen, PL||Shpall, EJ||Rezvani, K||Alousi, AM||Chemaly, RF||Shelburne, S||Vence, LM||Okhuysen, PC||Jensen, VB||Swennes, AG||McAllister, F||Marcelo Riquelme Sanchez, E||Zhang, Y||Le Chatelier, E||Zitvogel, L||Pons, N||Austin-Breneman, JL||Haydu, LE||Burton, EM||Gardner, JM||Sirmans, E||Hu, J||Lazar, AJ||Tsujikawa, T||Diab, A||Tawbi, H||Glitza, IC||Hwu, WJ||Patel, SP||Woodman, SE||Amaria, RN||Davies, MA||Gershenwald, JE||Hwu, P||Lee, JE||Zhang, J||Coussens, LM||Cooper, ZA||Futreal, PA||Daniel, CR||Ajami, NJ||Petrosino, JF||Tetzlaff, MT||Sharma, P||Allison, JP||Jenq, RR||Wargo, JA

publication date

  • January 2018