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.
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 Zhang  5 ,  Zhihai Qin  4 ,  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.
PMID: 30377557 DOI: 10.1080/2162402X.2018.1461303
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.
Products