Inverse role of distinct subsets and distribution of macrophage in lung cancer prognosis: a meta-analysis

BACKGROUND: Tumor-associated macrophages (TAMs) play a crucial role in the regulation of local inflammatory and immune response of tumor microenvironment, being associated with worse outcome of several solid tumors. But the prognostic value of tumor-infiltrating TAMs in lung cancer is still controversial. METHODS: We conduct a meta-analysis of 3055 patients in 21 studies searched from PubMed and Medline to investigate the correlation between tumor-infiltrating TAMs, including distinct TAM subsets and tissue distribution, and survival of lung cancer. Survival data were computed into odds ratios (ORs) and pooled using Mantel–Haenszel random-effect model. All statistical tests were two-sided. RESULTS: High density of tumor-infiltrating TAMs was significantly associated with worse overall survival (OS) at 3 years (OR = 2.45, 95% CI = 1.25 to 4.80, P = 0.009) and 5 years (OR = 2.04, 95% CI = 1.03 to 4.01, P = 0.04) of lung cancer. Results for disease free survival (DFS) were similar. M2 subset was associated with worse 3 year-OS and 5 year-OS, whereas M1 subset was associated with better 3-year OS and 5-year OS. Elevated TAM density in tumor stroma was associated with worse OS at 3 years and 5 years, while elevated TAMs in tumor islet/tumor stroma were associated with better OS at 3 years and 5 years. CONCLUSIONS: Increased tumor-infiltrating TAMs are associated with poor prognosis of lung cancer. M2 subset and TAMs in tumor stroma were associated with worse survival, while M1 subset and TAMs in tumor islet were associated with favorable survival of lung cancer.