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Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients

  1. Author:
    Davar, Diwakar
    Dzutsev, Amiran K.
    McCulloch, John A.
    Rodrigues,Richard
    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
    Vujkovic-Cvijin, Ivan
    Wang, Hong
    Borhani, Amir A.
    Schwartz, Marc B.
    Dubner, Howard M.
    Ernst, Scarlett J.
    Rose, Amy
    Najjar, Yana G.
    Belkaid, Yasmine
    Kirkwood, John M.
    Trinchieri,Giorgio
    Zarour, Hassane M.

  2. Author Address

    Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA.Univ Pittsburgh, UPMC Hillman Canc Ctr, Pittsburgh, PA 15213 USA.NCI, Lab Integrat Canc Immunol, Ctr Canc Res, Bethesda, MD 20892 USA.Frederick Natl Lab Canc Res, Basic Sci Program, Genet & Microbiome Core, Frederick, MD 21702 USA.Oregon State Univ, Coll Pharm, Corvallis, OR 97331 USA.NIAID, Lab Immune Syst Biol, NIH, Bethesda, MD 20892 USA.Univ Pittsburgh, UPMC Hillman Canc Ctr, Biostat Facil, Pittsburgh, PA 15213 USA.Univ Pittsburgh, Dept Radiol, Div Abdominal Imaging, Pittsburgh, PA 15213 USA.Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA.Univ Pittsburgh, Dept Immunol, Pittsburgh, PA 15213 USA.Tsinghua Univ, Sch Med, 1 Tsinghua Yuan, Beijing 100084, Peoples R China.
    1. Year: 2021
    2. Date: Feb 5
  2. Journal: Science
  3. AMER ASSOC ADVANCEMENT SCIENCE,
    1. 371
    2. 6529
    3. Pages: 595-602
  5. Type of Article: Article
  6. ISSN: 0036-8075
  1. Abstract:

    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.

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  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1126/science.abf3363
  3. PMID: 33542131
  4. PMCID: PMC8097968
  5. View record in Web of Science®
  6. WOS: 000615715300047

Library Notes

  1. Fiscal Year: FY2020-2021
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