Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.
Vancheswaran GopalakrishnanChristine N SpencerLuigi NeziAlexandre ReubenMiles C AndrewsT V KarpinetsP A PrietoDiego A VicenteKristi L HoffmanSpencer C WeiAlexandria P CogdillLi ZhaoCourtney W HudgensD S HutchinsonT ManzoM Petaccia de MacedoT CotechiniTapsi KumarWei-Shen ChenS M ReddyRobert A Szczepaniak SloaneJ Galloway-PenaH JiangP L ChenE J ShpallKatayoun RezvaniA M AlousiR F ChemalySamuel A Shelburne IiiL M VencePablo C OkhuysenV B JensenA G SwennesFlorencia McAllisterErick RiquelmeYu ZhangEmmanuelle Le ChatelierL ZitvogelNicolas PonsJacob L Austin-BrenemanL E HayduE M BurtonJulie M SimonE SirmansJ HuAlexander J F LazarTakahiro TsujikawaAdi DiabHussein A TawbiIsabella C Glitza OlivaWen-Jen HwuSapna Pradyuman PatelS E WoodmanR N AmariaMichael A DaviesJeffrey E GershenwaldPatrick HwuJeffrey E LeeJ ZhangLisa M CoussensZachary A CooperP Andrew FutrealC R DanielNadim J AjamiJoseph F PetrosinoMichael T TetzlaffPadmanee SharmaJames P AllisonRobert R JenqJennifer A WargoPublished in: Science (New York, N.Y.) (2017)
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.
Keyphrases
- end stage renal disease
- chronic kidney disease
- ejection fraction
- newly diagnosed
- patients undergoing
- peritoneal dialysis
- prognostic factors
- mouse model
- endothelial cells
- metabolic syndrome
- machine learning
- microbial community
- cell proliferation
- skeletal muscle
- small molecule
- cell therapy
- deep learning
- electronic health record
- wastewater treatment
- case control
- data analysis