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

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

doi:10.18632/oncotarget.24835

Abstract

BackgroundTumor-associated immune cells are prognostic in non-small cell lung cancer (NSCLC) but findings have been conflicting.ObjectivesTo determine the prognostic role of immune cells according to localization in NSCLC patients.MethodsA 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.ResultsWe 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).ConclusionTumor 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.

Highlights

Lung cancer is one of the most common malignancies globally, accounting for 1.5 million cases annually
Improved outcomes were seen with increased tumor dendritic cell (DC) (overall survival (OS) hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.44–0.68), natural killer (NK) cells (OS Hazard Ratios (HR) 0.45; 0.31–0.65), tumor associated macrophages (TAM) (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)
Given the presence of different macrophage phenotypes, we determined the prognostic effect of M1 and M2 macrophages (Table 1, Figure 2B, 2C) and found M1 macrophages was associated with improved OS in the tumor (HR 0.10; 0.05–0.19) stromal M1 and stroma (HR 0.63; 0.42–0.94)

Summary

Introduction

Lung cancer is one of the most common malignancies globally, accounting for 1.5 million cases annually. A major advance in the treatment of non-small cell lung cancer (NSCLC) has been the use www.oncotarget.com of immunotherapy, such as immune checkpoint inhibitors targeting cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death receptor-1 (PD-1) and programmed death receptor ligand-1 (PD-L1) [5]. Assessment according to localization of the immune cells in tumor parenchyma or stroma has been performed. This is based on the observed varied presence of these cells in the tissue compartments, and associated functional implications. Tumor-associated immune cells are prognostic in non-small cell lung cancer (NSCLC) but findings have been conflicting

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