Center for Microbiota and Immunological Diseases, Shanghai General Hospital, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China;
Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305.
Proc Natl Acad Sci U S A. 2018 Jan 2;115(1):157-161. doi: 10.1073/pnas.1712901115. Epub 2017 Dec 18.
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, , could largely rescue the mice from immunopathology without an apparent effect on antitumor immunity, and this effect may be dependent on regulatory T cells.
能够减弱免疫耐受的抗体已被用于有效治疗癌症,但它们也可能引发严重的自身免疫。为了研究这一点,我们将抗 CTLA-4 治疗与标准结肠炎模型相结合,使小鼠患上更严重的疾病。用抗生素万古霉素预处理会引发更严重、几乎致命的形式,表明微生物组中的革兰氏阳性成分具有缓解作用。然后,我们发现一种常用的益生菌 ,可以在不明显影响抗肿瘤免疫的情况下,在很大程度上使小鼠免于免疫病理学,并且这种作用可能依赖于调节性 T 细胞。