Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 115, Issue 1, Pages 157-161Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1712901115
Keywords
probiotics; Bifidobacterium; CTLA-4; immune checkpoint blockade; intestinal immunopathology
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Funding
- Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning
- Shanghai Pujiang Program
- Howard Hughes Medical Institute
- 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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