Th17 cell-derived IL-17A promoted tumor progression via STAT3/NF-κB/Notch1 signaling in non-small cell lung cancer
Authors: Zhen Zhang
Qianyi He
Ruijie Wang
Yi Zhang
Chaoqi Zhang
Xinfeng Chen
Bin Zhang
Li Yang
Liping Wang
Ruirui Wang
Zhihai Qin
Journal: OncoImmunology (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Th17 cells; Tumor microenvironment; interleukin-17A (IL-17A); non-small cell lung cancer (NSCLC); tumor progression.
Affiliations: Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China., Cancer Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China., Henan Key Laboratory for Tumor Immunology and Biotherapy, Zhengzhou, Henan 450052, P.R. China., Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China., Department of Hematology/Oncology, School of Medicine, Northwestern University, Chicago, IL60611, USA., 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. 

Retracted: No

PubPeer comments:
 #1 Dear Dr.u00a0Xu-Fengu00a0Huang, u00a0 Thank you for your attention to our research. In response to your questions, I use my colleagueu2019s account to reply. We have carefully checked the manuscript and our original data, and found our mistakesu00a0in Q1, Q2, and Q4. Now we have sent the Corrigendum materials to the editorial office of Oncoimmunology for correction.u00a0These corrections donu2019t change the results and conclusion. As foru00a0Q3 and Q5, because we used the same cells with the same treatment in one experiment, so the same representative pictures were shown. In the last question (Q6) you mentioned,u00a0b-actin,u00a0N-cadherinu00a0and OCT4 were simultaneously detected with the same samples in the western blot experiment. Therefore, the same internal referenceu00a0(b-actin)u00a0was used when displaying N-cadherin and OCT4. u00a0 Thank you for your comments again. u00a0 Best regards, u00a0 Ruirui Wang , 
 Hi, I am Dr Xu-Feng Huang from University of Wollongong Australia. Maybe we have the same name, but it was not me posted these comments. Please identify your self with your institution s name. I feel this is very odd who may have used my name to post these. Xu-Feng Huang , 
 Hi, Please use your own name to post your comments. Please do not use my name. Sincerely, Xu-Feng Huang University of Wollongong, Australia , 
 There are massive photo overlapping and duplications in this publication. Partially overlapping and photo duplication in Fig.2C (Left) and Fig.3B (Right). ![file] Photo duplication in Fig.2D (Left) and Fig.3E (Right) ![file] Photos representing different treatments are overlapped in Fig.3B. ![file] Photos representing different treatments are overlapped in Fig.3E. ![file] Photo duplication in Fig.4B (Left) and Fig.5A (Right) ![file] , 
 Despite having lots of photo duplications and overlaps, this publication was allowed to correct. But the statement of the authors on the correction is not persuading. Following is the statement:  When this article was published online, we noticed that Figure 2C, Figure 3B and Figure 3E were partially overlapped. The article has now been corrected and the correct figures are also included below . By the way, the authors should more carefully check their photos and data. So that they would not leave more flaws. In Fig. S3, photos from samples with different treatments are partially overlapped. ![file] Fig.4B and Fig. 5A, the H460 panels are identical. The authors had not changed them in the correction. In the response (See #2), the first author Wang said  the same cells with the same treatment in one experiment, so the same representative pictures were shown . I guess Fig.4B and Fig. 5A are belonged to this condition. But why the statistical values are different? The sphere number by IL17 treatment is less than 100 in Fig. 4B but is about 125 in Fig. 5C, which represents the statistical summary of Fig. 5A. Could the authors give a more reasonable explanation? ![file] ,