Work

IL-17A weakens the antitumor immuity by inhibiting apoptosis of MDSCs in Lewis lung carcinoma bearing mice

Year: 2016

Type: article

Abstract: // Juan Wang 1, 2, 4, * , Yue Zhang 1, * , Kai Yin 3, * , Peiqi Xu 2 , Jie Tian 2 , Jie Ma 2 , Xinyu Tian 2 , Yungang Wang 2 , Xinyi Tang 2 , Huaxi Xu 2 , Shengjun Wang 1, 2 1 Department of Laboratory Medicine, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, China 2 Institute of Laboratory Medicine, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China 3 Department of General Surgery, The Affiliated Hospital, Jiangsu University, Zhenjiang, China 4 Department of Laboratory Medicine, Changzhou TCM Hospital, Changzhou, China * These authors contributed equally to this work Correspondence to: Shengjun Wang, email: [email protected] Jie Tian, email: [email protected] Keywords: myeloid-derived suppressor cells, interleukin-17, apoptosis, tumor immunology Received: October 04, 2016 Accepted: December 07, 2016 Published: December 16, 2016 ABSTRACT 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.

Source: Oncotarget

DOI: 10.18632/oncotarget.13978