Cancer Immunology, Immunotherapy

, Volume 67, Issue 5, pp 713–727 | Cite as

Pretreatment neutrophil-to-lymphocyte ratio is associated with outcome of advanced-stage cancer patients treated with immunotherapy: a meta-analysis

  • Tao Jiang
  • Meng Qiao
  • Chao Zhao
  • Xuefei Li
  • Guanghui Gao
  • Chunxia Su
  • Shengxiang Ren
  • Caicun Zhou
Original Article



To investigate the association between pretreatment blood neutrophil-to-lymphocyte ratio (NLR) and clinical outcomes for advanced-stage cancer patients treated with immunotherapy.


We conducted a comprehensive literature search to assess the relationship between pretreatment blood NLR and overall survival (OS) or progression-free survival (PFS) in advanced-stage cancer patients treated with immunotherapy. Published data including hazard ratios (HRs) and related 95% confidence interval (CI) were extracted. Pooled estimates of treatment outcomes were calculated using RevMan 5.3.5.


Twenty-seven studies with 4647 patients were included in the current study. The pooled results suggested that high pretreatment blood NLR was correlated with significant shorter OS (HR = 1.98, 95% CI 1.66–2.36, P < 0.001) and PFS (HR = 1.78, 95% CI 1.48–2.15, P < 0.001). Subgroup analysis stratified by study targets revealed that anti-VEGF/VEGFR therapy (HR = 2.04, 95% CI 1.61–2.60, P < 0.001) and immune checkpoints blockade (HR = 2.16, 95% CI 1.86–2.51, P < 0.001) were significantly associated with inferior OS while other targets (HR = 1.63, 95% CI 0.89–2.99, P = 0.120) were not associated with OS. There was no correlation between distinct NLR cutoff values and OS (\({r^{{\text{Pearson}}}}\) = 0.218, P = 0.329) or PFS benefit (\({r^{{\text{Pearson}}}}\) = − 0.386, P = 0.140). Of note, HRs of PFS showed significant correlation with HRs of OS (\({r^{{\text{Pearson}}}}\) = 0.656, P = 0.015).


Elevated pretreatment blood NLR was a promising prognostic and predictive biomarker for advanced-stage cancer patients treated with immunotherapy.


Cancer Neutrophil-to-lymphocyte ratio Immunotherapy Biomarker Immune microenvironment 



American Society of Clinical Oncology


Confidence interval


European Society for Medical Oncology


Hazard ratio


Neutrophil-to-lymphocyte ratio


Preferred Reporting Items for Systematic Reviews and Meta-analyses statement


Statistical Package for Social Sciences


World Lung Cancer Conference




Author contributions

Tao Jiang and Caicun Zhou designed this study; Tao Jiang, Meng Qiao, Xuefei Li, Chao Zhao, Guanghui Gao, Chunxia Su and Shengxiang Ren collected the clinical data; Xuefei Li, Chao Zhao and Guanghui Gao performed the quality assessment; Tao Jiang, Meng Qiao and Shengxiang Ren performed statistical analyses; Caicun Zhou gave critical comments and suggestions; Tao Jiang and Shengxaing Ren drafted the manuscript; all authors approved the final version of the manuscript.


This study was supported in part by grants from the National Natural Science Foundation of China (No. 81672286 and 81402486), the Fundamental Research Funds for the Central Universities (No. 1511219041), key project of Shanghai Municipal Commission of Health and Family Planning (No. 2013zyjb0401), Shanghai Committee of Science and Technology (134119b1001) and Outstanding Young Doctor Program of Shanghai Municipal Commission of Health and Family Planning (No. XYQ2013097).

Compliance with ethical standards

Conflict of interest

The authors have declared no conflicts of interest.

Ethical approval and ethical standards


Informed consent


Animal source


Cell line authentication


Supplementary material

262_2018_2126_MOESM1_ESM.pdf (1.9 mb)
Supplementary material 1 (PDF 1903 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer InstituteTongji University School of MedicineShanghaiPeople’s Republic of China
  2. 2.Department of Lung Cancer and Immunology, Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiPeople’s Republic of China

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