Prognostic impact of tumor-associated macrophage infiltration in non-small cell lung cancer: A systemic review and meta-analysis

Tumor-associated macrophages (TAMs) are important components of cancer microenvironment. In the present study, we searched PubMed, Embase, Cochrane library and Web of Science to perform a meta-analysis of 20 studies including a total of 2,572 non-small cell lung cancer (NSCLC) patients, in order to determine the association between TAMs and NSCLC prognosis. The combined hazard ratio (HR) of 9 studies showed that the density of total CD68(+) TAMs in the tumor islet and stroma was not associated with overall survival (OS) of the patients. However, the pooled HR of 4 studies showed that high density of CD68(+) TAMs in the tumor islet predicted better OS, while the pooled HR of 6 studies showed that high density of CD68(+) TAMs in the tumor stroma was associated with poor OS. A high islet/stroma ratio of CD68(+) TAMs was associated with better OS. A high density of M1 TAMs in the tumor islet was associated with better OS, while a high density of M2 TAMs in the tumor stroma predicted poor OS. These findings suggest that, although the density of total CD68(+) TAMs is not associated with OS, the localization and M1/M2 polarization of TAMs are potential prognostic predictors of NSCLC.