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

Th17 细胞衍生的 IL-17A 通过 STAT3/NF-κB/Notch1 信号传导促进非小细胞肺癌中的肿瘤进展

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

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.

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