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微生物群引发STING-I型IFN依赖性单核细胞对肿瘤微环境的重编程
作者:小柯机器人 发布时间:2021/10/10 22:45:53

美国国家癌症研究所Romina S. Goldszmid小组发现,微生物群引发STING-I型IFN依赖性单核细胞对肿瘤微环境的重编程。2021年10月7日,《细胞》杂志在线发表了这项成果。

研究人员发现,微生物群信号使肿瘤微环境(TME)中的单核吞噬细胞向免疫刺激性单核细胞和树突状细胞(DC)方向发育。单细胞RNA测序显示,缺乏微生物群会使TME向促肿瘤性巨噬细胞倾斜。机制上,研究人员表明,微生物群衍生的STING(stimulator of interferon genes)激动剂诱导瘤内单核细胞产生I型干扰素(IFN-I),从而调节巨噬细胞极化和自然杀伤(NK)细胞-DC交流。用高纤维饮食调节微生物群可触发瘤内IFN-I-NK细胞-DC信号轴,并提高免疫检查点阻断(ICB)的疗效。

研究人员在接受ICB治疗的黑色素瘤患者中验证了这一发现,并表明预测的瘤内IFN-I和反应者与非反应者之间的免疫组成差异可通过粪便微生物群移植转移来实现。这项研究发现了微生物群和先天性TME之间的机理联系,并可以用来改善癌症治疗。

据悉,TME影响着癌症的发展和治疗反应。因此,了解什么能调节TME的免疫区域是至关重要的。

附:英文原文

Title: Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment

Author: Khiem C. Lam, Romina E. Araya, April Huang, Quanyi Chen, Martina Di Modica, Richard R. Rodrigues, Amélie Lopès, Sarah B. Johnson, Benjamin Schwarz, Eric Bohrnsen, Alexandria P. Cogdill, Catharine M. Bosio, Jennifer A. Wargo, Maxwell P. Lee, Romina S. Goldszmid

Issue&Volume: 2021-10-07

Abstract: The tumor microenvironment (TME) influences cancer progression and therapy response.Therefore, understanding what regulates the TME immune compartment is vital. Herewe show that microbiota signals program mononuclear phagocytes in the TME toward immunostimulatorymonocytes and dendritic cells (DCs). Single-cell RNA sequencing revealed that absenceof microbiota skews the TME toward pro-tumorigenic macrophages. Mechanistically, weshow that microbiota-derived stimulator of interferon genes (STING) agonists inducetype I interferon (IFN-I) production by intratumoral monocytes to regulate macrophagepolarization and natural killer (NK) cell-DC crosstalk. Microbiota modulation witha high-fiber diet triggered the intratumoral IFN-I-NK cell-DC axis and improved theefficacy of immune checkpoint blockade (ICB). We validated our findings in individualswith melanoma treated with ICB and showed that the predicted intratumoral IFN-I andimmune compositional differences between responder and non-responder individuals canbe transferred by fecal microbiota transplantation. Our study uncovers a mechanisticlink between the microbiota and the innate TME that can be harnessed to improve cancertherapies.

DOI: 10.1016/j.cell.2021.09.019

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)01066-7

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/