The association between monocytic myeloid-derived suppressor cells levels and the anti-tumor efficacy of anti-PD-1 therapy in NSCLC patients
The association between monocytic myeloid-derived suppressor cells levels and the anti-tumor efficacy of anti-PD-1 therapy in NSCLC patients
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NSCLC 患者中单核细胞骨髓源性抑制细胞水平与抗 PD-1 治疗的抗肿瘤疗效之间的关系
DOI：
10.1016/j.tranon.2020.100865
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发表时间：
2020-12-01
影响因子：
5
通讯作者：
Jiang, Jinjun
中科院分区：
文献类型：
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作者：
Feng, Jiuxing;Chen, Shujing;Jiang, Jinjun
单核细胞骨髓源性抑制细胞 (M-MDSC)、粒细胞 MDSC (G-MDSC) 和调节性 T 细胞 (Treg) 会抑制适应性抗肿瘤免疫并破坏抗 PD-1 治疗的疗效。然而，抗 PD-1 治疗对非小细胞肺癌 (NSCLC) 中这些免疫抑制细胞的影响尚未明确。在这项回顾性研究中，27名晚期NSCLC患者被分为部分缓解（PR）组、疾病稳定（SD）组和疾病进展（PD）组。通过流式细胞仪评估抗 PD-1 治疗对循环 Tregs、G-MDSC 和 M-MDSC 的影响。在这里，我们发现抗 PD-1 治疗可提高 NSCLC 患者的循环 Tregs 水平，这在前两个治疗周期中表现出最显着的增强。相比之下，抗 PD-1 治疗并没有总体改变 G-MDSC 和 M-MDSC 水平。然而，PR 组的 M-MDSC 基线水平较高，在第一个周期的抗 PD-1 治疗后表现出显着下降。此外，PR组的M-MDSCs水平在随后的治疗周期中维持在较低水平。一致地，在抗小鼠 PD-1 Ab 治疗后，同基因肿瘤模型中的 Tregs 水平急剧增加。因此，抗小鼠 ly6c Ab 中和 M-MDSC 增强了抗 PD-1 疗法在小鼠中的抗肿瘤功效。最后，PR 组和小鼠中 M-MDSC 水平的降低与效应 CD8(+) T 细胞扩增的增强有关。总之，抗PD-1治疗可上调NSCLC患者的Tregs水平，且M-MDSC水平与抗PD-1治疗的抗肿瘤疗效相关。 M-MDSC 的中和可能是增强 NSCLC 抗 PD-1 治疗效果的一个有前景的选择。
Monocyticmyeloid-derived suppressor cells (M-MDSCs), granulocytic MDSC (G-MDSCs) and regulatory T cells (Tregs) inhibit adaptive anti-tumor immunity and undermine the efficacy of anti-PD-1 therapy. However, the impact of anti-PD-1 treatment on these immunosuppressive cells has not been clearly defined in non-small cell lung cancer (NSCLC). In this retrospective study, 27 advanced NSCLC patients were divided into partial response (PR), stable disease (SD), and progressive disease (PD) groups. The impact of anti-PD-1 therapy on circulating Tregs, G-MDSCs, and M-MDSCs was assessed by flow cytometer. Here, we found that anti-PD-1 treatment boosted circulating Tregs levels, which presented the most remarkable augment during the first two therapeutic cycles, in NSCLC patients. In contrast, anti-PD-1 therapy did not overall change G-MDSCs and M-MDSCs levels. However, the PR group had a higher baseline level of M-MDSCs, which exhibited a significant decrease after the first cycle of anti-PD-1 treatment. Besides, M-MDSCs levels in the PR group were maintained at a low level in the following therapeutic cycles. Consistently, Tregs levels robustly increased in the syngeneic tumor model after anti-mouse PD-1 Ab treatment. Accordingly, M-MDSCs neutralization by anti-mouse ly6c Ab enhanced the anti-tumor efficacy of anti-PD-1 therapy in mice. Finally, the decreased M-MDSCs levels were associated with the enhanced effector CD8(+) T cells expansion in the PR group and mice. In conclusion, anti-PD-1 therapy upregulates Tregs levels in NSCLC patients, and the M-MDSC levels are associated with the antitumor efficacy of anti-PD-1 treatment. Neutralization of M-MDSCs may be a promising option to augment anti-PD-1 therapy efficacy in NSCLC.