c-Rel Is a Myeloid Checkpoint for Cancer Immunotherapy.
c-Rel Is a Myeloid Checkpoint for Cancer Immunotherapy.
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DOI：
10.1038/s43018-020-0061-3
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发表时间：
2020-05
期刊：
影响因子：
22.7
通讯作者：
Chen YH
中科院分区：
文献类型：
--
作者：
Li T;Li X;Zamani A;Wang W;Lee CN;Li M;Luo G;Eiler E;Sun H;Ghosh S;Jin J;Murali R;Ruan Q;Shi W;Chen YH
针对淋巴细胞检查站的免疫疗法在治愈癌症方面大有可为。然而，大多数癌症患者对这种形式的治疗没有反应。除了淋巴样细胞，髓系细胞在控制对癌症的免疫方面也起着至关重要的作用。是否存在可靶向治疗癌症的髓系检查点尚未得到很好的证实。在这里，我们展示了c-Rel，核因子B家族的成员，通过选择性地打开促肿瘤基因而通过c-Rel增强体关闭抗肿瘤基因来指定髓系来源的抑制细胞(MDSCs)的产生。小鼠髓系细胞中c-Rel缺乏明显抑制肿瘤生长，药物抑制c-Rel也有同样的作用。同时阻断c-rel和淋巴检查点蛋白PD1的联合疗法在治疗癌症方面比单独阻断两者都更有效。因此，c-Rel是一种髓系检查点，可作为治疗癌症的靶点。
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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