Th17 cell-derived IL-17A promoted tumor progression via STAT3/NF-κB/Notch1 signaling in non-small cell lung cancer

Ruirui Wang; Li Yang; Chaoqi Zhang; Ruijie Wang; Zhen Zhang; Qianyi He; Xinfeng Chen; Bin Zhang; Zhihai Qin; Liping Wang; Yi Zhang

doi:10.1080/2162402X.2018.1461303

Th17 cell-derived IL-17A promoted tumor progression via STAT3/NF-κB/Notch1 signaling in non-small cell lung cancer

Oncoimmunology. 2018 Aug 23;7(11):e1461303. doi: 10.1080/2162402X.2018.1461303. eCollection 2018.

Authors

Ruirui Wang^{1

2

3

4}, Li Yang^{1

2

3}, Chaoqi Zhang^{1

2

3}, Ruijie Wang^{1

2

3}, Zhen Zhang^{1

2

3}, Qianyi He^{1

2

3}, Xinfeng Chen^{1

2

3}, Bin Zhang⁵, Zhihai Qin⁴, Liping Wang^{2

3}, Yi Zhang^{1

2

3

6}

Affiliations

¹ Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
² Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
³ Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, Henan 450052, P.R. China.
⁴ Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
⁵ Department of Hematology/Oncology, School of Medicine, Northwestern University, Chicago, IL60611, USA.
⁶ School of Life Sciences, Zhengzhou University, Zhengzhou, Henan 450001, P.R. China.

Abstract

Non-small cell lung cancer (NSCLC) accounts for the majority of all lung cancer cases, which is the leading cause of cancer deaths worldwide. IL-17░A, the major effector cytokine derived from Th17 cells, is a key cytokine in tumor pathogenesis and modulates tumor progression. We aimed to identify whether IL-17░A derived from Th17 cells promotes the progression of NSCLC. Here we found that the level of Th17 cells was increased in NSCLC and IL-17░A was mainly produced by CD4⁺ cells (Th17 cells) in NSCLC. IL-17░A enhanced the migration, invasion and stemness of NSCLC via STAT3/NF-κB/Notch1 signaling. Blockade of this signaling inhibited the migration, invasion and stemness of NSCLC mediated by IL-17░A. Th17 cells in NSCLC were closely associated with poor prognosis of NSCLC patients. Our results indicated that Th17 cell-derived IL-17░A plays an important role in tumor progression of NSCLC via STAT3/NF-κB/Notch1 signaling. Therefore, therapeutic strategies against this pathway would be valuable to be developed for NSCLC treatment.

Keywords: Th17 cells; Tumor microenvironment; interleukin-17A (IL-17A); non-small cell lung cancer (NSCLC); tumor progression.

Publication types

Research Support, Non-U.S. Gov't

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (No.81171986, No. 81602024, No. 81771781), Funding from State's Key Project of Research and Development Plan (No. 2016YFC1303500), Research Grant from the Ministry of Public Health (No.201501004), Fundings for Creative Research Team of Henan Province, Creative Research Team of Higher Education of Henan Province.