Prognostic significance of immune cells in non-small cell lung cancer: meta-analysis

Ross A. Soo _, Zhaojin Chen, Rebecca Siew Yan Teng, Hon-Lyn Tan, Barry Iacopetta, Bee Choo Tai and Richie Soong

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Oncotarget. 2018; 9:24801-24820. https://doi.org/10.18632/oncotarget.24835

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Ross A. Soo1,2,5, Zhaojin Chen3, Rebecca Siew Yan Teng4, Hon-Lyn Tan1, Barry Iacopetta5, Bee Choo Tai3,6 and Richie Soong2,7

1Department of Haematology-Oncology, National University Health System, Singapore

2Cancer Science Institute of Singapore, National University of Singapore, Singapore

3Investigational Medicine Unit, National University Health System, Singapore

4Yong Loo Lin School of Medicine, National University of Singapore, Singapore

5School of Surgery, The University of Western Australia, Perth, Australia

6Saw Swee Hock School of Public Health, National University of Singapore, Singapore

7Department of Pathology, National University Health System, Singapore

Correspondence to:

Ross A. Soo, email: [email protected]

Keywords: non-small cell lung cancer; immune cells; dendritic cells; tumor associated macrophages; mast cells

Received: December 29, 2017     Accepted: March 06, 2018     Published: May 15, 2018


Background: Tumor-associated immune cells are prognostic in non-small cell lung cancer (NSCLC) but findings have been conflicting.

Objectives: To determine the prognostic role of immune cells according to localization in NSCLC patients.

Methods: A systematic literature review and meta-analysis was performed on dendritic cell (DC), tumor associated macrophages (TAM), mast cells (MC), natural killer (NK) cells, T and B cells and tumor CTLA-4 and PD-L1 studies.

Results: We analysed 96 articles (n= 21,752 patients). Improved outcomes were seen with increased tumor DCs (overall survival (OS) hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.44–0.68), NK cells (OS HR 0.45; 0.31–0.65), TAMs (OS HR 0.33; 0.17–0.62), M1 TAMs (OS HR 0.10; 0.05–0.21), CD3+ T cells (disease specific survival (DSS) HR 0.64; 0.48–0.86), CD8+ T cells (OS HR 0.78; 0.66–0.93), B cells (OS HR 0.65; 0.42–0.99) and with increased stroma DC (DSS HR 0.62; 0.47–0.83), NK cells (DSS HR 0.51; 0.32–0.82), M1 TAMs (OS HR 0.63; 0.42–0.94), CD4+ T cells (OS HR 0.45; 0.21–0.94), CD8+ T cells (OS HR 0.77; 0.69–0.86) and B cells (OS HR 0.74;0.56–0.99). Poor outcomes were seen with stromal M2 TAMs (OS HR 1.44; 1.06–1.96) and Tregs (relapse free survival (RFS) HR 1.80; 1.34–2.43). Tumor PD-L1 was associated with worse OS (1.40; 1.20–1.69), RFS (1.67) and DFS (1.24).

Conclusion: Tumor and stroma DC, NK cells, M1 TAMs, CD8+ T cells and B cells were associated with improved prognosis and tumor PD-L1, stromal M2 TAMs and Treg cells had poorer prognosis. Higher quality studies are required for confirmation.

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