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; Richie Soong

doi:10.18632/oncotarget.24835

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

Oncotarget. 2018 May 15;9(37):24801-24820. doi: 10.18632/oncotarget.24835.

Authors

Ross A Soo^{1

2

3}, Zhaojin Chen⁴, Rebecca Siew Yan Teng⁵, Hon-Lyn Tan¹, Barry Iacopetta³, Bee Choo Tai^{4

6}, Richie Soong^{2

7}

Affiliations

¹ Department of Haematology-Oncology, National University Health System, Singapore.
² Cancer Science Institute of Singapore, National University of Singapore, Singapore.
³ School of Surgery, The University of Western Australia, Perth, Australia.
⁴ Investigational Medicine Unit, National University Health System, Singapore.
⁵ Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
⁶ Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
⁷ Department of Pathology, National University Health System, Singapore.

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.

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