Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade.

Autor:	Andrews MC; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria, Australia.; Deparment of Medicine, Monash University, Melbourne, Victoria, Australia., Duong CPM; Gustave Roussy Cancer Campus (GRCC), Villejuif, France.; Institut National de la Santé Et de la Recherche Medicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine Kremlin-Bicêtre, Le Kremlin-Bicêtre, France., Gopalakrishnan V; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Iebba V; Gustave Roussy Cancer Campus (GRCC), Villejuif, France.; Institut National de la Santé Et de la Recherche Medicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France., Chen WS; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Dermatology, University of South Florida Morsani College of Medicine, Tampa, FL, USA., Derosa L; Gustave Roussy Cancer Campus (GRCC), Villejuif, France.; Institut National de la Santé Et de la Recherche Medicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine Kremlin-Bicêtre, Le Kremlin-Bicêtre, France., Khan MAW; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Cogdill AP; Gustave Roussy Cancer Campus (GRCC), Villejuif, France.; Institut National de la Santé Et de la Recherche Medicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine Kremlin-Bicêtre, Le Kremlin-Bicêtre, France.; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., White MG; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Wong MC; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Ferrere G; Gustave Roussy Cancer Campus (GRCC), Villejuif, France.; Institut National de la Santé Et de la Recherche Medicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine Kremlin-Bicêtre, Le Kremlin-Bicêtre, France., Fluckiger A; Gustave Roussy Cancer Campus (GRCC), Villejuif, France.; Institut National de la Santé Et de la Recherche Medicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine Kremlin-Bicêtre, Le Kremlin-Bicêtre, France., Roberti MP; Gustave Roussy Cancer Campus (GRCC), Villejuif, France.; Institut National de la Santé Et de la Recherche Medicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine Kremlin-Bicêtre, Le Kremlin-Bicêtre, France., Opolon P; Gustave Roussy Cancer Campus (GRCC), Villejuif, France., Alou MT; Gustave Roussy Cancer Campus (GRCC), Villejuif, France.; Institut National de la Santé Et de la Recherche Medicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine Kremlin-Bicêtre, Le Kremlin-Bicêtre, France., Yonekura S; Gustave Roussy Cancer Campus (GRCC), Villejuif, France.; Institut National de la Santé Et de la Recherche Medicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine Kremlin-Bicêtre, Le Kremlin-Bicêtre, France., Roh W; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Spencer CN; Department of Informatics, Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA., Curbelo IF; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Vence L; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Reuben A; Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Johnson S; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Arora R; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Morad G; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Lastrapes M; MD Anderson Cancer Center University of Texas Health Graduate School of Biomedical Sciences (GSBS), Houston, TX, USA., Baruch EN; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Little L; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Gumbs C; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Cooper ZA; AstraZeneca, Gaithersburg, MD, USA., Prieto PA; Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA., Wani K; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Lazar AJ; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Tetzlaff MT; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Hudgens CW; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Callahan MK; Department of Informatics, Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Adamow M; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Division of Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Postow MA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Division of Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Ariyan CE; Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Gaudreau PO; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Nezi L; Istituto Europeo di Oncologia, Milan, Italy., Raoult D; Aix-Marseille Université, MEPHI, IRD, IHU Méditerranée Infection, Marseille, France., Mihalcioiu C; Department of Medicine, Faculty of Medicine and Health Sciences, McGill University Health Centre, Montreal, Quebec, Canada., Elkrief A; Cedars Cancer Center, McGill University Health Centre, Montreal, Quebec, Canada., Pezo RC; Division of Medical Oncology, University of Toronto, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada., Haydu LE; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Simon JM; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Tawbi HA; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., McQuade J; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Hwu P; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Hwu WJ; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Amaria RN; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Burton EM; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Woodman SE; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Watowich S; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Diab A; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Patel SP; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Glitza IC; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Wong MK; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zhao L; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Zhang J; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Ajami NJ; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Petrosino J; Department of Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA., Jenq RR; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Davies MA; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Gershenwald JE; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Futreal PA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Sharma P; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Allison JP; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Routy B; Gustave Roussy Cancer Campus (GRCC), Villejuif, France.; Institut National de la Santé Et de la Recherche Medicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.; Université Paris-Saclay, Faculté de Médecine Kremlin-Bicêtre, Le Kremlin-Bicêtre, France., Zitvogel L; Gustave Roussy Cancer Campus (GRCC), Villejuif, France. laurence.zitvogel@gustaveroussy.fr.; Institut National de la Santé Et de la Recherche Medicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France. laurence.zitvogel@gustaveroussy.fr.; Université Paris-Saclay, Faculté de Médecine Kremlin-Bicêtre, Le Kremlin-Bicêtre, France. laurence.zitvogel@gustaveroussy.fr., Wargo JA; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. jwargo@mdanderson.org.; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. jwargo@mdanderson.org.
Jazyk:	angličtina
Zdroj:	Nature medicine [Nat Med] 2021 Aug; Vol. 27 (8), pp. 1432-1441. Date of Electronic Publication: 2021 Jul 08.
DOI:	10.1038/s41591-021-01406-6
Abstrakt:	Treatment with combined immune checkpoint blockade (CICB) targeting CTLA-4 and PD-1 is associated with clinical benefit across tumor types, but also a high rate of immune-related adverse events. Insights into biomarkers and mechanisms of response and toxicity to CICB are needed. To address this, we profiled the blood, tumor and gut microbiome of 77 patients with advanced melanoma treated with CICB, with a high rate of any ≥grade 3 immune-related adverse events (49%) with parallel studies in pre-clinical models. Tumor-associated immune and genomic biomarkers of response to CICB were similar to those identified for ICB monotherapy, and toxicity from CICB was associated with a more diverse peripheral T-cell repertoire. Profiling of gut microbiota demonstrated a significantly higher abundance of Bacteroides intestinalis in patients with toxicity, with upregulation of mucosal IL-1β in patient samples of colitis and in pre-clinical models. Together, these data offer potential new therapeutic angles for targeting toxicity to CICB. (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze:	MEDLINE
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