The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time

Junliang Ma,Fuqiang Dai,Lunxu Liu,Zongbing You,Nanbin Yu,Guowei Che

doi:10.1186/1471-2407-10-112

Abstract

BackgroundTumor-associated macrophages (TAMs) play an important role in growth, progression and metastasis of tumors. In non-small cell lung cancer (NSCLC), TAMs' anti-tumor or pro-tumor role is not determined. Macrophages are polarized into M1 (with anti-tumor function) and M2 (with pro-tumor function) forms. This study was conducted to determine whether the M1 and M2 macrophage densities in NSCLC are associated with patient's survival time.MethodsFifty patients with an average of 1-year survival (short survival group) and 50 patients with an average of 5-year survival (long survival group) were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical double-staining of CD68/HLA-DR (markers for M1 macrophages) and CD68/CD163 (markers for M2 macrophages) was performed and evaluated in a blinded fashion. The M1 and M2 macrophage densities in the tumor islets, stroma, or islets and stroma were determined using computer-aided microscopy. Correlation of the macrophage densities and patient's survival time was analyzed using the Statistical Package for the Social Sciences.ResultsApproximately 70% of TAMs were M2 macrophages and the remaining 30% were M1 macrophages in NSCLC. The M2 macrophage densities (approximately 78 to 113 per mm2) in the tumor islets, stroma, or islets and stroma were not significantly different between the long survival and short survival groups. The M1 macrophage densities in the tumor islets (approximately 70/mm2) and stroma (approximately 34/mm2) of the long survival group were significantly higher than the M1 macrophage densities in the tumor islets (approximately 7/mm2) and stroma (13/mm2) of the short survival group (P < 0.001 and P < 0.05, respectively). The M2 macrophage densities were not associated with patient's survival time. The M1 macrophage densities in the tumor islets, stroma, or islets and stroma were positively associated with patient's survival time in a univariate analysis (P < 0.01 or 0.001). In a multivariate Cox proportional hazards analysis, the M1 macrophage density in the tumor islets was an independent predictor of patient's survival time.ConclusionsThe M1 macrophage density in the tumor islets is an independent predictor of survival time in NSCLC patients.

Highlights

Tumor-associated macrophages (TAMs) play an important role in growth, progression and metastasis of tumors
Immunohistochemical detection of macrophages In order to assess whether the markers chosen detect different cellular subsets of macrophages, tissue sections from five patients were initially stained for CD68, CD163, or human leukocyte antigen (HLA)-DR, alone or in combination
When the M1 and M2 macrophages were assessed in the tumor islets or stroma individually, the M1 macrophage densities in the tumor islets and stroma of the long survival group were significantly higher than the M1 macrophage densities in the tumor islets and stroma

Summary

Introduction

Tumor-associated macrophages (TAMs) play an important role in growth, progression and metastasis of tumors. In non-small cell lung cancer (NSCLC), TAMs’ anti-tumor or pro-tumor role is not determined. Macrophages are polarized into M1 (with anti-tumor function) and M2 (with pro-tumor function) forms. This study was conducted to determine whether the M1 and M2 macrophage densities in NSCLC are associated with patient’s survival time. Non-small cell lung cancer (NSCLC) remains the most common cause of cancer-related death worldwide. The interaction between the tumor cells and stromal cells in the tumor microenvironment plays an important role in tumor growth and metastasis. Macrophages are prominent stromal cells in this interaction. They secret a variety of growth factors, cytokines, chemokines, and enzymes that regulate tumor growth, angiogenesis, invasion, and metastasis [2]

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