Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL.
The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL.
J Exp Med. 2020 May 4;217(5). doi: 10.1084/jem.20192282.
Most studies focus on how intestinal microbiota influence cancer immunotherapy through activating gut immunity. However, immunotherapies related to innate responses such as CD47 blockade rely on the rapid immune responses within the tumor microenvironment. Using one defined anaerobic gut microbiota to track whether microbiota interact with host immunity, we observed that Bifidobacterium facilitates local anti-CD47 immunotherapy on tumor tissues through the capacity to accumulate within the tumor microenvironment. Systemic administration of Bifidobacterium leads to its accumulation within the tumor and converts the nonresponder mice into responders to anti-CD47 immunotherapy in a stimulator of interferon genes (STING)- and interferon-dependent fashion. Local delivery of Bifidobacterium potently stimulates STING signaling and increases cross-priming of dendritic cells after anti-CD47 treatment. Our study identifies the mechanism by which gut microbiota preferentially colonize in tumor sites and facilitate immunotherapy via STING signaling.
大多数研究都集中在肠道微生物群如何通过激活肠道免疫来影响癌症免疫疗法。然而，与 CD47 阻断等先天反应相关的免疫疗法依赖于肿瘤微环境中的快速免疫反应。我们使用一种定义明确的厌氧肠道微生物群来跟踪微生物群是否与宿主免疫相互作用，观察到双歧杆菌通过在肿瘤微环境中积累的能力促进肿瘤组织上的局部抗 CD47 免疫疗法。双歧杆菌的全身给药导致其在肿瘤内积累，并以干扰素基因刺激物 (STING) 和干扰素依赖的方式将非应答者小鼠转化为抗 CD47 免疫疗法的应答者。局部递送双歧杆菌可强烈刺激 STING 信号，并在抗 CD47 治疗后增加树突状细胞的交叉呈递。我们的研究确定了肠道微生物群优先在肿瘤部位定植并通过 STING 信号促进免疫疗法的机制。
