Regulatory T cells (Tregs) play a pivotal role in the inhibition of anti-tumor immune responses. Understanding the mechanisms governing Treg homeostasis may therefore be important for development of effective tumor immunotherapy. We have recently demonstrated a key role for the canonical nuclear factor κB (NF-κB) subunits, p65 and c-Rel, in Treg identity and function. In this report, we show that NF-κB c-Rel ablation specifically impairs the generation and maintenance of the activated Treg (aTreg) subset, which is known to be enriched at sites of tumors. Using mouse models, we demonstrate that melanoma growth is drastically reduced in mice lacking c-Rel, but not p65, in Tregs. Moreover, chemical inhibition of c-Rel function delayed melanoma growth by impairing aTreg-mediated immunosuppression and potentiated the effects of anti-PD-1 immunotherapy. Our studies therefore establish inhibition of NF-κB c-Rel as a viable therapeutic approach for enhancing checkpoint-targeting immunotherapy protocols.

中文翻译：

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NF-κBc-Rel对于癌症的调节性T细胞免疫检查点至关重要。

调节性T细胞（Tregs）在抑制抗肿瘤免疫反应中起关键作用。因此，了解控制Treg稳态的机制对于开发有效的肿瘤免疫疗法可能很重要。我们最近证明了规范核因子κB（NF-κB）亚基p65和c-Rel在Treg身份和功能中的关键作用。在本报告中，我们显示NF-κBc-Rel消融特异性地损害了活化的Treg（aTreg）子集的生成和维持，该子集已知在肿瘤部位富集。使用小鼠模型，我们证明在Tregs中缺乏c-Rel而不是p65的小鼠中黑色素瘤的生长急剧减少。此外，通过抑制aTreg介导的免疫抑制作用，化学抑制c-Rel功能可延迟黑色素瘤的生长，并增强抗PD-1免疫疗法的作用。