التفاصيل البيبلوغرافية
| العنوان: |
Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients. |
| المؤلفون: |
Davar, Diwakar, Dzutsev, Amiran K., McCulloch, John A., Rodrigues, Richard R., Chauvin, Joe-Marc, Morrison, Robert M., Deblasio, Richelle N., Menna, Carmine, Ding, Quanquan, Pagliano, Ornella, Zidi, Bochra, Zhang, Shuowen, Badger, Jonathan H., Vetizou, Marie, Cole, Alicia M., Fernandes, Miriam R., Prescott, Stephanie, Costa, Raquel G. F., Balaji, Ascharya K., Morgun, Andrey |
| المصدر: |
Science. 2/5/2021, Vol. 371 Issue 6529, p595-602. 8p. 4 Diagrams. |
| مصطلحات موضوعية: |
*FECAL microbiota transplantation, *THERAPEUTIC use of bacteria, *MELANOMA treatment, *PROTEOMICS, *MOLECULAR biology |
| مستخلص: |
Anti–programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti–PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti–PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti–PD-1 in patients with PD-1–refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti–PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8– expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti–PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti–PD-1 in a subset of PD-1 advanced melanoma. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |