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

// Ross A. Soo 1, 2, 5 , Zhaojin Chen 3 , Rebecca Siew Yan Teng 4 , Hon-Lyn Tan 1 , Barry Iacopetta 5 , Bee Choo Tai 3, 6 and Richie Soong 2, 7 1 Department of Haematology-Oncology, National University Health System, Singapore 2 Cancer Science Institute of Singapore, National University of Singapore, Singapore 3 Investigational Medicine Unit, National University Health System, Singapore 4 Yong Loo Lin School of Medicine, National University of Singapore, Singapore 5 School of Surgery, The University of Western Australia, Perth, Australia 6 Saw Swee Hock School of Public Health, National University of Singapore, Singapore 7 Department of Pathology, National University Health System, Singapore Correspondence to: Ross A. Soo, email: ross_soo@nuhs.edu.sg 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 ABSTRACT 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.