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

Juan Wang,Xinyi Tang,Jie Tian,Peiqi Xu,Kai Yin,Yungang Wang,Huaxi Xu,Jie Ma,Shengjun Wang,Xinyu Tian,Yue Zhang

doi:10.18632/oncotarget.13978

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.

Highlights

Immune responses play important roles in preventing tumor development and invasion
We found the survival rate of Myeloid-derived suppressor cells (MDSCs) increased with IL-17 treatment, especially at the concentration of 5 μg/L (Figure 1B–1C)
They found that IL-6 further promotes tumor growth, which is dependent on the STAT3 signaling pathway [30]

Summary

Introduction

Immune responses play important roles in preventing tumor development and invasion. Organism immunity defends against inflammation and tumors. It suppresses the abnormal enhancement of autoimmune responses. What’s more, in the process from inflammation to tumor, myeloid-derived suppressor cells (MDSCs) increase in the peripheral blood, spleens, and tumor sites. MDSCs represent the immature population of myeloid cells, which are composed of macrophages, dendritic cells, and granulocytes [2]. This immature population plays an important role in escaping from organism antitumor immunity by inducing regulatory T cells and restraining the activation and proliferation of effector T cells [3,4]. Previous reports have suggested a number of cytokines and transcription factors can influence the differentiation, activation, and expansion of MDSCs [5,6,7,8]

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Results

Conclusion