Chemokine Receptor CXCR3 Correlates with Decreased M2 Macrophage Infiltration and Favorable Prognosis in Gastric Cancer.

Fangfang Chen,Honglin Yan,Jingping Yuan,Shuai Yin,Huan Liu

doi:10.1155/2019/6832867

Abstract

Aim The aim of this study was to explore the correlation of chemokine receptor CXCR3 with M2 macrophage infiltration, various clinicopathological features, and prognosis in patients diagnosed with gastric cancer (GC). Methods Expression of CXCR3 protein and M2 macrophage was evaluated in 156 GC patients and corresponding paracancerous tissues by immunohistochemical (IHC) analysis. Results In our study, 59 (37.82%) showed high expression of CXCR3 protein in 156 GC tissues. Expression of CXCR3 protein was significantly increased in tumor tissues compared with corresponding paracancerous tissues (P < 0.001). Overexpression of CXCR3 protein correlated with decreased M2 macrophage infiltration (P = 0.001). By analyzing the association between expression of CXCR3 protein and clinicopathological factors of GC patients, we found that high level of CXCR3 protein was significantly correlated with better differentiation (P =0.017), I/II TNM stage (P = 0.02), and smaller invasion depth (P = 0.003). Moreover, we found through Kaplan-Meier analysis and log-rank test that GC patients with high expression of CXCR3 protein and low M2 macrophage infiltration had better overall survival (OS) and low mortality rate (P < 0.001 and P = 0.024, respectively). The multivariate survival analysis showed that high expression of CXCR3 protein could serve as a favorable independent biomarker for prognosis in GC patients [hazard ratio (HR): 0.342 (0.204-0.571); P < 0.001]. Conclusion Our study indicates that overexpression of CXCR3 protein in GC is associated with decreased M2 macrophage infiltration and improved OS and thus can be further exploited as a biomarker in GC.

Highlights

Gastric cancer (GC) is by far the fifth most common malignant tumors all over the world and has high mortality: it was the third-leading cause of cancer-related deaths worldwide [1]
We evaluated the association of CXCR3 protein expression with macrophage infiltration, clinicopathologic characteristics, and prognosis in GC patients
We reported that the overexpression of CXCR3 protein in GC is associated with decreased M2 macrophage infiltration and a relatively better prognosis

Summary

Introduction

Gastric cancer (GC) is by far the fifth most common malignant tumors all over the world and has high mortality: it was the third-leading cause of cancer-related deaths worldwide [1]. The prognosis of the GC is significantly correlated with the tumor-associated immune cells in tumor immune microenvironment [2]. Tumor-associated immune cells such as natural killer (NK) cells, dendritic (DC) cells, helper T1 (Th1) cells, and cytotoxic CD8 cells in the tumor microenvironment are generally correlated with favorable outcome [3,4,5,6]. Infiltration of B cells, regulatory T (Tregs) cells, and Th2 and Th17 cells promotes tumor development and correlates with a poor prognosis [7,8,9]. The M1 macrophages can induce apoptosis, reduce proliferation of tumor cells, and inhibit the development of neovascularization. M2 macrophages can promote both tumor growth and metastasis and predict a poor prognosis [11,12,13]

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