Distribution of M1 and M2 macrophages in tumor islets and stroma in relation to prognosis of non-small cell lung cancer

Jurgita Jackute,Simona Vaitkiene,Raimundas Sakalauskas,Brigita Sitkauskiene,Marius Zemaitis,Skaidrius Miliauskas,Darius Pranys

doi:10.1186/s12865-018-0241-4

Jurgita Jackute, Simona Vaitkiene + Show 5 more

Open Access

https://doi.org/10.1186/s12865-018-0241-4

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Journal: BMC Immunology	Publication Date: Jan 24, 2018
Citations: 171	License type: open-access

Affiliation: Lithuanian University of Health Sciences

Abstract

BackgroundNon-small cell lung cancer (NSCLC) remains the most common cause of cancer related death worldwide. Tumor-infiltrating macrophages are believed to play an important role in growth, progression, and metastasis of tumors. In NSCLC, the role of macrophages remains controversial; therefore, we aimed to evaluate the distribution of macrophages (M1 and M2) in tumor islets and stroma and to analyze their relations to patients’ survival.MethodsLung tissue specimens from 80 NSCLC patients who underwent surgical resection for NSCLC (pathological stage I-III) and 16 control group subjects who underwent surgery because of recurrent spontaneous pneumothorax were analyzed. Immunohistochemical double staining of CD68/iNOS (markers for M1 macrophages) and CD68/CD163 (markers for M2 macrophages) was performed and evaluated in a blinded manner. The numbers of M1 and M2 macrophages in tumor islets and stroma were counted manually.ResultsPredominant infiltration of M1 and M2 macrophages was observed in the tumor stroma compared with the tumor islets. M2 macrophages predominated over M1 macrophages in the tumor tissue. Tumor islets-infiltrating M1 macrophages and the number of total tumor-infiltrating M2 macrophages were independent predictors of patients survival: high infiltration of M1 macrophages in tumor islets was associated with increased overall survival in NSCLC (P < 0.05); high infiltration of total M2 macrophages in tumor (islets and stroma) was associated with reduced overall survival in NSCLC (P < 0.05).ConclusionsThis study demonstrated that high infiltration of M1 macrophages in the tumor islets and low infiltration of total tumor-infiltrating M2 macrophages were associated with improved NSCLC patients’ survival.Trial registrationClinicalTrials.gov NCT01955343, registered on September 27, 2013

Highlights

Non-small cell lung cancer (NSCLC) remains the most common cause of cancer related death worldwide
We observed a greater number of lung tissue-infiltrating M1 and M2 macrophages in NSCLC patients compared with the control group (P < 0.001; Fig. 4)
In agreement with the data from this study, our results revealed that the number of M1 and M2 macrophages was significantly higher in the tumor tissue than in the lung tissue from the control group

Summary

Introduction

Non-small cell lung cancer (NSCLC) remains the most common cause of cancer related death worldwide. Tumor-infiltrating macrophages are believed to play an important role in growth, progression, and metastasis of tumors. In NSCLC, the role of macrophages remains controversial; we aimed to evaluate the distribution of macrophages (M1 and M2) in tumor islets and stroma and to analyze their relations to patients’ survival. Lung cancer remains the most common cancer type worldwide and it is the leading cause of cancer death. Macrophages are abundant among tumorinfiltrating innate and adaptive immune cells and are present at all stages of tumor progression. Experimental murine models and clinical studies indicate that tumor-infiltrating macrophages generally play a protumorigenic role [5].

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