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

abstract

  • 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.

authors

  • Gopalakrishnan, V
  • Spencer, CN
  • Nezi, L
  • Reuben, A
  • Andrews, Miles
  • 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
  • Sloane, R Szczepaniak
  • 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
  • Sanchez, E Marcelo Riquelme
  • 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

  • 2018