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https://ahro.austin.org.au/austinjspui/handle/1/26983| Title: | Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade. | Austin Authors: | Andrews, Miles C;Duong, Connie P M;Gopalakrishnan, Vancheswaran;Iebba, Valerio;Chen, Wei-Shen;Derosa, Lisa;Khan, Md Abdul Wadud;Cogdill, Alexandria P;White, Michael G;Wong, Matthew C;Ferrere, Gladys;Fluckiger, Aurélie;Roberti, Maria P;Opolon, Paule;Alou, Maryam Tidjani;Yonekura, Satoru;Roh, Whijae;Spencer, Christine N;Curbelo, Irina Fernandez;Vence, Luis;Reuben, Alexandre;Johnson, Sarah;Arora, Reetakshi;Morad, Golnaz;Lastrapes, Matthew;Baruch, Erez N;Little, Latasha;Gumbs, Curtis;Cooper, Zachary A;Prieto, Peter A;Wani, Khalida;Lazar, Alexander J;Tetzlaff, Michael T;Hudgens, Courtney W;Callahan, Margaret K;Adamow, Matthew;Postow, Michael A;Ariyan, Charlotte E;Gaudreau, Pierre-Olivier;Nezi, Luigi;Raoult, Didier;Mihalcioiu, Catalin;Elkrief, Arielle;Pezo, Rossanna C;Haydu, Lauren E;Simon, Julie M;Tawbi, Hussein A;McQuade, Jennifer;Hwu, Patrick;Hwu, Wen-Jen;Amaria, Rodabe N;Burton, Elizabeth M;Woodman, Scott E;Watowich, Stephanie;Diab, Adi;Patel, Sapna P;Glitza, Isabella C;Wong, Michael K;Zhao, Li;Zhang, Jianhua;Ajami, Nadim J;Petrosino, Joseph;Jenq, Robert R;Davies, Michael A;Gershenwald, Jeffrey E;Futreal, P Andrew;Sharma, Padmanee;Allison, James P;Routy, Bertrand;Zitvogel, Laurence;Wargo, Jennifer A | Affiliation: | Aix-Marseille Université, MEPHI, IRD, IHU Méditerranée Infection, Marseille, France 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 Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA La Trobe University School of Cancer Medicine, Heidelberg, Victoria, Australia Deparment of Medicine, Monash University, Melbourne, Victoria, Australia Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Department of Informatics, Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA MD Anderson Cancer Center University of Texas Health Graduate School of Biomedical Sciences (GSBS), Houston, TX, USA AstraZeneca, Gaithersburg, MD, USA Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Department of Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA Department of Dermatology, University of South Florida Morsani College of Medicine, Tampa, FL, USA Université Paris-Saclay, Faculté de Médecine Kremlin-Bicêtre, Le Kremlin-Bicêtre, France Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA Division of Immunology, Memorial Sloan Kettering Cancer Center, New York, NY, USA Istituto Europeo di Oncologia, Milan, Italy Department of Medicine, Faculty of Medicine and Health Sciences, McGill University Health Centre, Montreal, Quebec, Canada Cedars Cancer Center, McGill University Health Centre, Montreal, Quebec, Canada Division of Medical Oncology, University of Toronto, Sunnybrook Odette Cancer Centre, Toronto, Ontario, Canada Olivia Newton-John Cancer Research Institute |
Issue Date: | 8-Jul-2021 | Date: | 2021-07-08 | Publication information: | Nature Medicine 2021; 27(8): 1432-1441 | Abstract: | 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. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/26983 | DOI: | 10.1038/s41591-021-01406-6 | ORCID: | 0000-0003-1231-8641 0000-0002-9067-8557 0000-0002-0716-306X 0000-0003-0527-2964 0000-0001-5022-5505 0000-0001-5788-6840 0000-0003-4047-3016 0000-0002-7395-9939 0000-0003-3441-4095 0000-0003-4510-0382 0000-0002-9460-618X 0000-0003-1059-0940 0000-0002-6395-4499 0000-0001-8312-7485 0000-0002-9087-0012 0000-0002-7709-0126 0000-0002-4670-7656 0000-0002-0633-5974 0000-0003-1942-851X 0000-0002-2393-2172 0000-0001-6876-278X 0000-0003-1969-659X 0000-0001-5412-9860 0000-0002-0977-0912 0000-0001-8663-2671 0000-0003-4658-055X 0000-0003-1596-0998 0000-0003-3438-7576 |
Journal: | Nature Medicine | PubMed URL: | 34239137 | Type: | Journal Article |
| Appears in Collections: | Journal articles |
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