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

Jiandong Mei,Feng Lin,Chengwu Liu,Lunxu Liu,Chenglin Guo,Zongbing You,Qiang Pu,Hu Liao,Zhilan Xiao,Lin Ma

doi:10.18632/oncotarget.9079

Jiandong Mei, Feng Lin + Show 8 more

Open Access

https://doi.org/10.18632/oncotarget.9079

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Abstract

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.

Highlights

Lung cancer is the most common cause of cancerrelated deaths in both men and women worldwide [1]
The combined hazard ratio (HR) of 9 studies showed that the density of total CD68+ Tumor-associated macrophages (TAMs) in the tumor islet and stroma was not associated with overall survival (OS) of the patients
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

Summary

Introduction

Lung cancer is the most common cause of cancerrelated deaths in both men and women worldwide [1]. New therapeutic modalities, such as minimally invasive surgery and targeted therapy, have been introduced to the treatment of lung cancer during the past decades. Tumor-associated macrophages (TAMs) are an important component of the tumor microenvironment [5, 6] This group of immune cells function as immune regulators in the tumor microenvironment and are potential targets of cancer immunotherapy [7]. Activation of M2 macrophages induces Th2 responses and promotes tissue repair and remodeling, angiogenesis, and immune suppression, as well as tumor progression [11, 13, 14]

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