@article{96622c891b1842dbaa16d3fa23dee688,
title = "Diet-driven microbial ecology underpins associations between cancer immunotherapy outcomes and the gut microbiome",
abstract = "The gut microbiota shapes the response to immune checkpoint inhibitors (ICIs) in cancer, however dietary and geographic influences have not been well-studied in prospective trials. To address this, we prospectively profiled baseline gut (fecal) microbiota signatures and dietary patterns of 103 trial patients from Australia and the Netherlands treated with neoadjuvant ICIs for high risk resectable metastatic melanoma and performed an integrated analysis with data from 115 patients with melanoma treated with ICIs in the United States. We observed geographically distinct microbial signatures of response and immune-related adverse events (irAEs). Overall, response rates were higher in Ruminococcaceae-dominated microbiomes than in Bacteroidaceae-dominated microbiomes. Poor response was associated with lower fiber and omega 3 fatty acid consumption and elevated levels of C-reactive protein in the peripheral circulation at baseline. Together, these data provide insight into the relevance of native gut microbiota signatures, dietary intake and systemic inflammation in shaping the response to and toxicity from ICIs, prompting the need for further studies in this area.",
author = "Simpson, {Rebecca C.} and Shanahan, {Erin R.} and Marcel Batten and Reijers, {Irene L.M.} and Mark Read and Silva, {Ines P.} and Versluis, {Judith M.} and Rosilene Ribeiro and Angelatos, {Alexandra S.} and Jian Tan and Chandra Adhikari and Menzies, {Alexander M.} and Saw, {Robyn P.M.} and Maria Gonzalez and Shannon, {Kerwin F.} and Spillane, {Andrew J.} and Rebecca Velickovic and Lazar, {Alexander J.} and Damania, {Ashish V.} and Mishra, {Aditya K.} and Manoj Chelvanambi and Anik Banerjee and Ajami, {Nadim J.} and Wargo, {Jennifer A.} and Laurence Macia and Holmes, {Andrew J.} and Wilmott, {James S.} and Blank, {Christian U.} and Scolyer, {Richard A.} and Long, {Georgina V.}",
note = "Funding Information: We thank G. Giles of the Cancer Epidemiology Division, Cancer Council Victoria, for permission to use the Cancer Council Victoria Dietary Questionnaire for Epidemiological Studies (DQES v3.2), Melbourne, Australia, 1996. We acknowledge the technical assistance provided by the Sydney Informatics Hub, a core research facility of the University of Sydney. G.V.L and R.A.S are supported by NHMRC Program Grant R.A.S is supported by an NHMRC Practitioner Fellowship and G.V.L by an NHMRC Investigator Grant. G.V.L is also supported by the University of Sydney Medical Foundation. Support from the Cameron Family and Ainsworth Foundation, as well as from colleagues at Melanoma Institute Australia, Royal Prince Alfred Hospital and NSW Health Pathology is gratefully acknowledged. E.R.S. acknowledges financial support from the The William Arthur Martin {\`a} Beckett Cancer Research Trust (University of Sydney Fellowship). Funding support was provided by a Tour de Cure Australia project grant (RSP-00054-19/20) (R.A.S, M.B., E.R.S). Funding Information: We thank G. Giles of the Cancer Epidemiology Division, Cancer Council Victoria, for permission to use the Cancer Council Victoria Dietary Questionnaire for Epidemiological Studies (DQES v3.2), Melbourne, Australia, 1996. We acknowledge the technical assistance provided by the Sydney Informatics Hub, a core research facility of the University of Sydney. G.V.L and R.A.S are supported by NHMRC Program Grant R.A.S is supported by an NHMRC Practitioner Fellowship and G.V.L by an NHMRC Investigator Grant. G.V.L is also supported by the University of Sydney Medical Foundation. Support from the Cameron Family and Ainsworth Foundation, as well as from colleagues at Melanoma Institute Australia, Royal Prince Alfred Hospital and NSW Health Pathology is gratefully acknowledged. E.R.S. acknowledges financial support from the The William Arthur Martin {\`a} Beckett Cancer Research Trust (University of Sydney Fellowship). Funding support was provided by a Tour de Cure Australia project grant (RSP-00054-19/20) (R.A.S, M.B., E.R.S). Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
month = nov,
doi = "10.1038/s41591-022-01965-2",
language = "English (US)",
volume = "28",
pages = "2344--2352",
journal = "Nature medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "11",
}