Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients
| العنوان: | Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients |
|---|---|
| المؤلفون: | Yang Xie, Laura A. Coughlin, Arthur E. Frankel, Andrew Y. Koh, Eugene P. Frenkel, Jiwoong Kim, Thomas W. Froehlich |
| المصدر: | Neoplasia: An International Journal for Oncology Research, Vol 19, Iss 10, Pp 848-855 (2017) |
| بيانات النشر: | Elsevier, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, biology, Melanoma, Faecalibacterium prausnitzii, Ipilimumab, Pembrolizumab, Gut flora, biology.organism_classification, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, Immune checkpoint, 3. Good health, 03 medical and health sciences, 030104 developmental biology, Immunology, parasitic diseases, medicine, Microbiome, Nivolumab, medicine.drug |
| الوصف: | This is the first prospective study of the effects of human gut microbiota and metabolites on immune checkpoint inhibitor (ICT) response in metastatic melanoma patients. Whereas many melanoma patients exhibit profound response to ICT, there are fewer options for patients failing ICT—particularly with BRAF-wild-type disease. In preclinical studies, specific gut microbiota promotes regression of melanoma in mice. We therefore conducted a study of the effects of pretreatment gut microbiota and metabolites on ICT Response Evaluation Criteria in Solid Tumors response in 39 metastatic melanoma patients treated with ipilimumab, nivolumab, ipilimumab plus nivolumab (IN), or pembrolizumab (P). IN yielded 67% responses and 8% stable disease; P achieved 23% responses and 23% stable disease. ICT responders for all types of therapies were enriched for Bacteroides caccae . Among IN responders, the gut microbiome was enriched for Faecalibacterium prausnitzii, Bacteroides thetaiotamicron , and Holdemania filiformis . Among P responders, the microbiome was enriched for Dorea formicogenerans . Unbiased shotgun metabolomics revealed high levels of anacardic acid in ICT responders. Based on these pilot studies, both additional confirmatory clinical studies and preclinical testing of these bacterial species and metabolites are warranted to confirm their ICT enhancing activity. |
| اللغة: | English |
| تدمد: | 1522-8002 1476-5586 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7a71ec9138719aa0ca8e4e4cb24af1c6 http://www.sciencedirect.com/science/article/pii/S1476558617302385 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7a71ec9138719aa0ca8e4e4cb24af1c6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15228002 14765586 |
|---|