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Plasma cytokines interleukin-18 and C-X-C motif chemokine ligand 10 are indicative of the anti-programmed cell death protein-1 treatment response in lung cancer patients

  • Wang, Yida1, 2
  • Chen, Hanxiao3
  • Zhang, Tianzhuo1
  • Yang, Xue3
  • Zhong, Jia3
  • Wang, Yuyan3
  • Chi, Yujia3
  • Wu, Meina3
  • An, Tongtong3
  • Li, Jianjie3
  • Zhao, Xinghui3
  • Dong, Zhi3
  • Wang, Ziping3
  • Zhao, Jun3
  • Zhuo, Minglei3
  • Huang, Jing1, 2
  • 1 and NHC Key Laboratory of Medical Immunology (Peking University), Beijing , (China)
  • 2 Chinese Academy of Medical Sciences, Beijing , (China)
  • 3 Peking University Cancer Hospital & Institute, Beijing , (China)
Published Article
Annals of Translational Medicine
AME Publishing Company
Publication Date
Jan 01, 2021
DOI: 10.21037/atm-20-1513
PMID: 33553326
PMCID: PMC7859784
PubMed Central


Background Although programmed cell death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) checkpoint inhibitors have shown prominent efficacy for treatment of advanced lung cancer, the outcomes of metastatic lung cancer remain poor throughout the world. Although progression-free survival (PFS) and overall survival (OS) have improved in the first- and second-line therapy settings for advanced lung cancer, the response rates to PD-1/PD-L1 inhibition range from 20% to 40%. Furthermore, patients may be at risk for immune-related adverse events (irAEs); hence, appropriate patient selection is crucial. This study aimed to identify a panel of plasma cytokines representing prognostic and predictive biomarkers of the response to anti-PD-1/PD-L1 treatment. Methods We prospectively studied 32 lung cancer patients who received anti-PD-1/PD-L1 antibody immunotherapy. Plasma cytokines in peripheral blood samples were evaluated and analyzed using flow cytometry at the time of diagnosis and at 2 months after the initiation of PD-1/PD-L1 inhibition. Results The baseline plasma concentrations of interleukin-18 (IL-18) and C-X-C motif chemokine ligand 10 (CXCL10) were correlated with the degree of tumor response. Moreover, the magnitude of plasma IL-18 and CXCL10 level fluctuations were correlated significantly with the objective tumor response to anti-PD-1/PD-L1 immunotherapy, and patients with high CXCL10 expression had significantly shorter PFS than those with low CXCL10 expression. A strong positive correlation between the fluctuation of IL-18 and interleukin-8 (IL-8) levels was detected, as was a negative correlation between the fluctuation of IL-18 and CXCL10 levels. The level of plasma C-C motif chemokine ligand 5 (CCL5) was significantly higher in patients with irAEs than in those without irAEs. Conclusions Plasma cytokines are related to the clinical efficacy of PD-1/PD-L1 inhibitors. IL-18 and CXCL10 are potential predictive markers for anti-PD-1/PD-L1 therapy in lung cancer patients and may play an important role in selecting patients who would benefit from PD-1/PD-L1 inhibitors.

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