4.8 Article

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

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.1712901115

Keywords

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

Funding

  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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