Lactobacillus rhamnosus GG Orchestrates an Antitumor Immune Response.
Lactobacillus rhamnosus GG Orchestrates an Antitumor Immune Response.
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DOI：
10.1016/j.jcmgh.2021.06.001
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发表时间：
2021
影响因子：
7.2
通讯作者：
Jones RM
中科院分区：
文献类型：
--
作者：
Owens JA;Saeedi BJ;Naudin CR;Hunter-Chang S;Barbian ME;Eboka RU;Askew L;Darby TM;Robinson BS;Jones RM
在结直肠癌中，大约95%的患者由于抗肿瘤免疫应答低而对免疫疗法难治。因此，迫切需要开发增加抗肿瘤免疫应答并降低肿瘤负荷以增强免疫疗法的治疗。肠道微生物组被描述为免疫反应的主要调节剂。我们给小鼠施用了人的唾液酸，鼠李糖乳杆菌GG（LGG），并表征了肠道免疫景观的变化。由于肠道微生物组中乳酸杆菌的存在与肿瘤负荷降低和抗肿瘤免疫反应有关，我们还用LGG补充了小鼠肠癌的遗传和化学模型。为了临床相关性，我们在肿瘤形成后治疗性地施用LGG。我们还测试了在LGG介导的肠道肿瘤负荷调节中对CD 8 T细胞的需求。我们检测到增加结肠CD 8 T细胞反应，特别是在LGG补充小鼠。CD 8 T细胞诱导依赖于通过Toll样受体-2介导的树突状细胞活化，从而描述了一种新的机制，其中人类微生物组的成员诱导肠道CD 8 T细胞应答。我们还表明，LGG通过CD 8 T细胞依赖性方式降低小鼠肠道癌模型中的肿瘤负荷。这些数据支持LGG在结直肠癌患者中增强抗肿瘤免疫应答的潜在用途，并最终增加免疫治疗的广度和疗效。
In colorectal cancer, approximately 95% of patients are refractory to immunotherapy because of low antitumor immune responses. Therefore, there is an exigent need to develop treatments that increase antitumor immune responses and decrease tumor burden to enhance immunotherapy. The gut microbiome has been described as a master modulator of immune responses. We administered the human commensal, Lactobacillus rhamnosus GG (LGG), to mice and characterized the changes in the gut immune landscape. Because the presence of lactobacilli in the gut microbiome has been linked with decreased tumor burden and antitumor immune responses, we also supplemented a genetic and a chemical model of murine intestinal cancer with LGG. For clinical relevance, we therapeutically administered LGG after tumors had formed. We also tested for the requirement of CD8 T cells in LGG-mediated modulation of gut tumor burden. We detected increased colonic CD8 T-cell responses specifically in LGG-supplemented mice. The CD8 T-cell induction was dependent on dendritic cell activation mediated via Toll-like receptor-2, thereby describing a novel mechanism in which a member of the human microbiome induces an intestinal CD8 T-cell response. We also show that LGG decreased tumor burden in the murine gut cancer models by a CD8 T-cell–dependent manner. These data support the potential use of LGG to augment antitumor immune responses in colorectal cancer patients and ultimately for increasing the breadth and efficacy of immunotherapy.
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影响因子：
5.8
作者：
Jia L;Wu R;Han N;Fu J;Luo Z;Guo L;Su Y;Du J;Liu Y
通讯作者：
Liu Y
影响因子：
45.3
作者：
Overman, Michael J.;Lonardi, Sara;Andre, Thierry
通讯作者：
Andre, Thierry
影响因子：
8.8
作者：
Jones RM;Desai C;Darby TM;Luo L;Wolfarth AA;Scharer CD;Ardita CS;Reedy AR;Keebaugh ES;Neish AS
通讯作者：
Neish AS
DOI：
10.1126/science.aao3290
发表时间：
2018-01-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Matson V;Fessler J;Bao R;Chongsuwat T;Zha Y;Alegre ML;Luke JJ;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
28.3
作者：
Lee, Se-Hoon;Cho, Sung-Yup;Park, Hansoo
通讯作者：
Park, Hansoo