加拿大卡尔加里大学Kathy D. McCoy和Lukas F. Mager研究组合作取得最新进展。他们发现生物组肌苷调节检查点抑制的免疫治疗反应。该研究于2020年8月13号发表于《科学》。

他们分离了三种细菌，包括假双歧杆菌、约翰逊乳杆菌和Olsenella菌种，它们在四种小鼠癌症模型中显著增强了免疫检查点抑制效应。他们发现，肠道假单胞菌通过代谢产物肌苷的产生，增强免疫疗法应答。免疫疗法诱导的肠屏障功能降低，增加了肌苷和活化的抗肿瘤T细胞的全身性易位。肌苷的作用取决于腺苷A2A受体的T细胞表达，并需要共同刺激。

总的来说，他们的研究确定了一种新的微生物代谢物-免疫途径，该途径可通过免疫疗法激活，可用于开发基于微生物的辅助疗法。

研究人员表示，几种肠道细菌与检查点封锁免疫疗法的效应增强相关，但微生物组增强抗肿瘤免疫力的潜在机制尚不清楚。

附：英文原文

Title: Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy

Author: Lukas F. Mager, Regula Burkhard, Nicola Pett, Noah C. A. Cooke, Kirsty Brown, Hena Ramay, Seungil Paik, John Stagg, Ryan A. Groves, Marco Gallo, Ian A. Lewis, Markus B. Geuking, Kathy D. McCoy

Issue&Volume: 2020/08/13

Abstract: Abstract Several species of intestinal bacteria have been associated with enhanced efficacy of checkpoint blockade immunotherapy, but the underlying mechanisms by which the microbiome enhances anti-tumor immunity is unclear. Here, we isolated three bacterial species, including Bifidobacterium pseudolongum, Lactobacillus johnsonii and Olsenella species, that significantly enhanced efficacy of immune checkpoint inhibitors in four mouse models of cancer. We found that intestinal B. pseudolongum modulated enhanced immunotherapy response through production of the metabolite inosine. Decreased gut barrier function induced by immunotherapy increased systemic translocation of inosine and activated anti-tumor T cells. The effect of inosine was dependent on T cell expression of the adenosine A2A receptor and required co-stimulation. Collectively, our study identifies a novel microbial metabolite-immune pathway that is activated by immunotherapy that may be exploited to develop microbial-based adjuvant therapies.

DOI: 10.1126/science.abc3421

Source: https://science.sciencemag.org/content/early/2020/08/12/science.abc3421