CD47 blockade triggers T cell–mediated destruction of immunogenic tumors, Nature Medicine 21,1209–1215(2015)
发布时间：2015年10月16日
Nature Medicine 21,1209–1215(2015)doi:10.1038/nm.3931
CD47 blockade triggers T cell–mediated destruction of immunogenic tumors
Xiaojuan Liu, Yang Pu, Kyle Cron, Liufu Deng, Justin Kline, William A Frazier, Hairong Xu, Hua Peng, Yang-Xin Fu & Meng Michelle Xu
Abstract
Macrophage phagocytosis of tumor cells mediated by CD47-specific blocking antibodies has been proposed to be the major effector mechanism in xenograft models. Here, using syngeneic immunocompetent mouse tumor models, we reveal that the therapeutic effects of CD47 blockade depend on dendritic cell but not macrophage cross-priming of T cell responses. The therapeutic effects of anti-CD47 antibody therapy were abrogated in T cell–deficient mice. In addition, the antitumor effects of CD47 blockade required expression of the cytosolic DNA sensor STING, but neither MyD88 nor TRIF, in CD11c+ cells, suggesting that cytosolic sensing of DNA from tumor cells is enhanced by anti-CD47 treatment, further bridging the innate and adaptive responses. Notably, the timing of administration of standard chemotherapy markedly impacted the induction of antitumor T cell responses by CD47 blockade. Together, our findings indicate that CD47 blockade drives T cell–mediated elimination of immunogenic tumors.
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CD47 blockade triggers T cell–mediated destruction of immunogenic tumors, Nature Medicine 21,1209–1215(2015)
Nature Medicine 21,1209–1215(2015)doi:10.1038/nm.3931
CD47 blockade triggers T cell–mediated destruction of immunogenic tumors
Xiaojuan Liu, Yang Pu, Kyle Cron, Liufu Deng, Justin Kline, William A Frazier, Hairong Xu, Hua Peng, Yang-Xin Fu & Meng Michelle Xu
Abstract
Macrophage phagocytosis of tumor cells mediated by CD47-specific blocking antibodies has been proposed to be the major effector mechanism in xenograft models. Here, using syngeneic immunocompetent mouse tumor models, we reveal that the therapeutic effects of CD47 blockade depend on dendritic cell but not macrophage cross-priming of T cell responses. The therapeutic effects of anti-CD47 antibody therapy were abrogated in T cell–deficient mice. In addition, the antitumor effects of CD47 blockade required expression of the cytosolic DNA sensor STING, but neither MyD88 nor TRIF, in CD11c+ cells, suggesting that cytosolic sensing of DNA from tumor cells is enhanced by anti-CD47 treatment, further bridging the innate and adaptive responses. Notably, the timing of administration of standard chemotherapy markedly impacted the induction of antitumor T cell responses by CD47 blockade. Together, our findings indicate that CD47 blockade drives T cell–mediated elimination of immunogenic tumors.
相关报道：http://www.ibp.cas.cn/kyjz/zxdt/201508/t20150818_4412265.html
文章链接：http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3931.html