4.8 Article

Bifidobacterium can mitigate intestinal immunopathology in the context of CTLA-4 blockade

出版社

NATL ACAD SCIENCES
DOI: 10.1073/pnas.1712901115

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probiotics; Bifidobacterium; CTLA-4; immune checkpoint blockade; intestinal immunopathology

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  1. Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning
  2. Shanghai Pujiang Program
  3. Howard Hughes Medical Institute
  4. Parker Institute for Cancer Immunotherapy

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Antibodies that attenuate immune tolerance have been used to effectively treat cancer, but they can also trigger severe autoimmunity. To investigate this, we combined anti-CTLA-4 treatment with a standard colitis model to give mice a more severe form of the disease. Pretreatment with an antibiotic, vancomycin, provoked an even more severe, largely fatal form, suggesting that a Gram-positive component of the microbiota had a mitigating effect. We then found that a commonly used probiotic, Bifidobacterium, could largely rescue the mice from immunopathology without an apparent effect on antitumor immunity, and this effect may be dependent on regulatory T cells.

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