Immunotherapy that targets lymphoid cell checkpoints holds great promise for curing cancer. However, many 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 kappa-light-chain-enhancer of activated B cells (NF-κB) family, specified the generation of myeloid-derived suppressor cells by selectively turning on protumoral genes while switching off antitumoral 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 programmed cell death protein 1 was more effective in treating cancer than blocking either alone. Thus, c-Rel is a myeloid checkpoint that can be targeted for treating cancer.

针对淋巴样细胞检查点的免疫疗法对治愈癌症有很大的希望。然而，许多癌症患者对这种形式的治疗没有反应。除淋巴细胞外，骨髓细胞在控制对癌症的免疫力方面也发挥着重要作用。是否存在可以靶向治疗癌症的骨髓检查点尚不明确。在这里，我们显示 c-Rel 是活化 B 细胞 (NF-κB) 家族的核因子 kappa-轻链增强子的成员，通过在关闭前选择性地打开促肿瘤基因来指定髓源抑制细胞的产生通过 c-Rel 增强体的抗肿瘤基因。骨髓细胞中的 c-Rel 缺乏显着抑制了小鼠的癌症生长，并且药物抑制 c-Rel 具有相同的效果。阻断 c-Rel 和淋巴检查点蛋白程序性细胞死亡蛋白 1 的联合疗法在治疗癌症方面比单独阻断任何一种疗法更有效。因此，c-Rel 是一个可以靶向治疗癌症的骨髓检查点。