Oral administration of Bifidobacterium breve promotes antitumor efficacy via dendritic cells-derived interleukin 12.
Oral administration of Bifidobacterium breve promotes antitumor efficacy via dendritic cells-derived interleukin 12.
复制标题
口服短双歧杆菌通过树突状细胞衍生的白细胞介素12来提高抗肿瘤功效。
DOI：
10.1080/2162402x.2020.1868122
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发表时间：
2021-01-15
期刊：
影响因子：
7.2
通讯作者：
Guo C
中科院分区：
文献类型：
--
作者：
Li Q;Li Y;Wang Y;Xu L;Guo Y;Wang Y;Wang L;Guo C
近年来，免疫治疗作为多学科治疗的一部分，逐渐受到人们的重视。然而，只有一小部分对该疗法敏感的患者能从中获益。越来越多的研究表明，肠道微生物群可以提高癌症免疫治疗的效率。双歧杆菌作为主要的益生菌之一，具有重要的免疫调节作用，已被动物研究和人体临床研究所证实。但具体的机制还没有明确阐明。本研究发现，口服短双歧杆菌（b.b breve） lw01可显著抑制肿瘤生长，上调肿瘤细胞凋亡，其作用机制依赖于肿瘤浸润淋巴细胞和树突状细胞（dc）在肿瘤微环境中的募集，而鼠李糖乳杆菌（L. rhamnosus） CGMCC 1.3724和大肠杆菌（e.c oli） MG1655则无此作用。在原位结扎肠袢模型中，短芽胞杆菌的刺激引发dc相关趋化因子CCL20的上调表达，并在肠绒毛中募集更多的dc。进一步的研究表明，树突状细胞分泌的白细胞介素12 （IL-12）的增强对短芽孢杆菌的抗肿瘤作用至关重要，而IL-12中和抗体的处理可以抵消这种作用。同时，外源性短芽胞杆菌对肠道菌群的调节可能会增强其抗肿瘤作用。本研究提供了一种简单易行的通过短芽孢杆菌促进抗肿瘤免疫的方法。
Recent advances in immunotherapy, as a part of the multidisciplinary therapy, has gradually gained more attention. However, only a small proportion of patients who sensitive to the therapy could gain benefits. An increasing number of studies indicate that intestinal microbiota could enhance the efficiency of cancer immunotherapy. As one of the main probiotics, Bifidobacterium plays an important role in immune regulation, which has been proved by animal research and human clinical study. But the detailed mechanism was not clearly elucidated. Here we found oral administration of Bifidobacterium breve (B. breve) lw01 could significantly inhibit tumor growth and up-regulate tumor cell apoptosis, which relied on the recruitment of tumor-infiltrating lymphocytes and dendritic cells (DCs) in tumor microenvironment, but not Lactobacillus rhamnosus (L. rhamnosus) CGMCC 1.3724 or Escherichia coli (E. coli) MG1655. In the in situ ligated intestine loop model, B. breve’s stimulation triggered the upregulated expression of DC-related chemokine CCL20 and recruited more DCs in the intestinal villi. Further study revealed the enhancement of interleukin 12 (IL-12) secretion derived from DCs is essential to B. breve’s antitumor effect, which was counteracted by the treatment of neutralizing antibody for IL-12. Meanwhile, the modulation of intestinal microbiota caused by exogenous B. breve might enhance its antitumor effect. This study provides a simple and easy way to promote antitumor immunity via B. breve.