Li Qingxiang, Li Yuke, Wang Yifei, Xu Le, Guo Yuxing, Wang Yixiang, Wang Lin, Guo Chuanbin
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China.
Department of Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, China.
Oncoimmunology. 2021 Jan 15;10(1):1868122. doi: 10.1080/2162402X.2020.1868122.
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, 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 () 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 () CGMCC 1.3724 or () MG1655. In the ligated intestine loop model, '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 's antitumor effect, which was counteracted by the treatment of neutralizing antibody for IL-12. Meanwhile, the modulation of intestinal microbiota caused by exogenous might enhance its antitumor effect. This study provides a simple and easy way to promote antitumor immunity via .
免疫疗法作为多学科治疗的一部分,近年来取得的进展逐渐受到更多关注。然而,只有一小部分对该疗法敏感的患者能够从中获益。越来越多的研究表明,肠道微生物群可以提高癌症免疫疗法的疗效。作为主要益生菌之一,在免疫调节中发挥着重要作用,这已得到动物研究和人体临床研究的证实。但其详细机制尚未明确阐明。在此,我们发现口服()lw01可显著抑制肿瘤生长并上调肿瘤细胞凋亡,这依赖于肿瘤微环境中肿瘤浸润淋巴细胞和树突状细胞(DCs)的募集,但()CGMCC 1.3724或()MG1655则无此作用。在结扎肠袢模型中,的刺激触发了DC相关趋化因子CCL20表达上调,并在肠绒毛中募集了更多DCs。进一步研究表明,DCs分泌的白细胞介素12(IL-12)增强对的抗肿瘤作用至关重要,而IL-12中和抗体处理可抵消这种作用。同时,外源性引起的肠道微生物群调节可能会增强其抗肿瘤作用。本研究提供了一种通过促进抗肿瘤免疫的简单易行方法。