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Impact of gefitinib in early stage treatment on circulating cytokines and lymphocytes for patients with advanced non–small cell lung cancer

Authors Sheng J, Fang W, Liu X, Xing S, Zhan J, Ma Y, Huang Y, Zhou N, Zhao H, Zhang L

Received 5 May 2016

Accepted for publication 26 August 2016

Published 21 February 2017 Volume 2017:10 Pages 1101—1110

DOI https://doi.org/10.2147/OTT.S112158

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ru Chen

Peer reviewer comments 5

Editor who approved publication: Prof. Dr. Geoffrey Pietersz

Jin Sheng,1–3,* Wenfeng Fang,1–3,* Xia Liu,3 Shan Xing,1,2,4 Jianhua Zhan,1,2 Yuxiang Ma,1,2 Yan Huang,1–3 Ningning Zhou,1–3 Hongyun Zhao,1–3 Li Zhang1–3

1State Key Laboratory of Oncology in South China, 2Collaborative Innovation Center for Cancer Medicine, 3Department of Medical Oncology, 4Department of Clinical Laboratory, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China

*These authors contributed equally to this work

Objectives: The impact of epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) on the human immune system remains undefined. This study illustrates the immunomodulatory effect of gefitinib in patients with advanced non-small cell lung cancer (NSCLC) and its relevant prognostic significance.
Patients and methods: Peripheral blood samples were collected from 54 patients at baseline and after 4 weeks of gefitinib treatment. Circulating lymphocyte populations and cytokine levels were measured. Pilot investigation of the impact of gefitinib on programmed cell death ligand-1 (PD-L1) expression was conducted by immunohistochemistry (IHC).
Results and conclusion: A significant increase of peripheral natural killer cells and interferon-gamma (INF-γ) after 4 weeks of gefitinib treatment (P=0.005 and 0.02, respectively). In addition, circulating interleukin (IL)-6 was significantly decreased, especially in patients sensitive to gefitinib (P<0.001). Higher levels of IL-6 at baseline independently correlated with poorer progression-free survival. Experiments with NSCLC specimens illustrated that PD-L1 expression were downregulated after 4 weeks of gefitinib treatment. In summary, it was found that gefitinib treatment can alter circulating cytokines and lymphocytes. Dynamic changes of circulating lymphocytes, cytokines, and even PD-L1 IHC expression around gefitinib treatment support the specific immunomodulatory effect of this agent for advanced NSCLC.

Keywords: non-small cell lung cancer, gefitinib, PD-L1, lymphocyte, cytokine

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