髓样
癌症研究
癌症免疫疗法
免疫疗法
癌症
癌细胞
生物
靶向治疗
髓源性抑制细胞
免疫学
抑制器
遗传学
作者
Ting Li,Xinyuan Li,Ali Zamani,Wei Wang,Chin-Nien Lee,Mingyue Li,George Luo,Emily Eiler,Honghong Sun,Sankar Ghosh,Jian Jin,Ramachandran Murali,Qingguo Ruan,Weiyun Shi,Youhai H. Chen
出处
期刊:Nature cancer
[Springer Nature]
日期:2020-05-18
卷期号:1 (5): 507-517
被引量:48
标识
DOI:10.1038/s43018-020-0061-3
摘要
Immunotherapy that targets lymphoid cell checkpoints holds great promise for curing cancer. However, a majority of cancer patients do not respond to this form of therapy. In addition to lymphoid cells, myeloid cells play essential roles in controlling immunity to cancer. Whether myeloid checkpoints exist that can be targeted to treat cancer is not well established. Here we show that c-Rel, a member of the nuclear factor (NF)-B family, specified the generation of myeloid-derived suppressor cells (MDSCs) by selectively turning on pro-tumoral genes while switching off anti-tumoral genes through a c-Rel enhanceosome. c-Rel deficiency in myeloid cells markedly inhibited cancer growth in mice, and pharmaceutical inhibition of c-Rel had the same effect. Combination therapy that blocked both c-Rel and the lymphoid checkpoint protein PD1 was more effective in treating cancer than blocking either alone. Thus, c-Rel is a myeloid checkpoint that can be targeted for treating cancer.
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