IL-17A weakens the antitumor immuity by inhibiting apoptosis of MDSCs in Lewis lung carcinoma bearing mice.
IL-17A weakens the antitumor immuity by inhibiting apoptosis of MDSCs in Lewis lung carcinoma bearing mice.
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IL-17A通过抑制Lewis肺癌荷瘤小鼠MDSCs凋亡削弱抗肿瘤免疫力
DOI：
10.18632/oncotarget.13978
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发表时间：
2017-01-17
期刊：
影响因子：
--
通讯作者：
Wang S
中科院分区：
文献类型：
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作者：
Wang J;Zhang Y;Yin K;Xu P;Tian J;Ma J;Tian X;Wang Y;Tang X;Xu H;Wang S
髓源性抑制细胞（MDSC）通过抑制效应T细胞活性和病理部位免疫抑制因子的产生来减弱抗肿瘤免疫应答。已经证实白细胞介素-17 A（IL-17 A）在促进炎症和肿瘤形成方面具有显著作用，并且IL-17已经涉及增强MDSC的免疫抑制，从而促进肿瘤进展。对这种关系的详细研究仍然是难以捉摸的。在我们的研究中，我们不仅证实了IL-17对刘易斯肺癌（LLC）发展的促进作用，而且还令人惊讶地显示IL-17可以通过激活ERK 1/2来延长MDSC的命运并增强其免疫抑制作用。此外，IL-17对MDSC的作用被逆转，甚至在肿瘤中通过阻断ERK 1/2也是如此。阻断ERK 1/2信号分子可增加MDSCs的凋亡，减弱MDSCs的抑制活性，从而部分恢复抗肿瘤免疫。因此，这些发现为IL-17和下游信号传导因子ERK 1/2对MDSC的重要性提供了新的见解。
Myeloid-derived suppressor cells (MDSCs) weaken the antitumor immune response through the inhibition of effector T cell activity and the production of immunosuppressive factors in pathological sites. It is well established that interleukin-17A (IL-17A) has a remarkable role on the promotion of inflammation and tumor formation, and IL-17 has been implicated in the enhancement of immunosuppression of MDSCs, which consequently promotes tumor progression. A detailed study of this relationship remains elusive. In our study, we not only confirmed the promotion of IL-17 on Lewis lung carcinoma (LLC) development but also surprisingly showed that IL-17 could extend the fate and enhance the immunosuppressive effect of MDSCs through activating ERK1/2. Additionally, the effect of IL-17 on MDSCs was reversed, even in tumors by blocking ERK1/2. Interdicting the signaling molecule ERK1/2 could increase the apoptosis of MDSCs and weaken the suppressive activity of MDSCs, so that thereafter, the antitumor immunity could be restored partly. Therefore, these findings offer new insights into the importance of IL-17 and the downstream signaling factor ERK1/2 for MDSCs.