Prognostic Value of CXCR2 in Breast Cancer.

Florence Boissière-Michot,Sophie Gourgou,Gwendal Lazennec,Colin Timaxian,William Jacot,Julien Fraisse

doi:10.3390/cancers12082076

Abstract

The tumor microenvironment appears essential in cancer progression and chemokines are mediators of the communication between cancer cells and stromal cells. We have previously shown that the ligands of the chemokine receptor CXCR2 were expressed at higher levels in triple-negative breast cancers (TNBC). Our hypothesis was that CXCR2 expression could also be altered in breast cancer. Here, we have analyzed the potential role of CXCR2 in breast cancer in a retrospective cohort of 105 breast cancer patients. Expression of CXCR2, CD11b (a marker of granulocytes) and CD66b (a marker of neutrophils) was analyzed by immunohistochemistry on tumor samples. We demonstrated that CXCR2 stained mainly stromal cells and in particular neutrophils. CXCR2, CD11b and CD66b expression were correlated with high grade breast cancers. Moreover, TNBC displayed a higher expression of CXCR2, CD11b and CD66b than hormone receptor positive or Her2 positive tumors. High levels of CXCR2 and CD11b, but not CD66b, were associated with a higher infiltration of T lymphocytes and B lymphocytes. We also observed a correlation between CXCR2 and AP-1 activity. In univariate analyses, CXCR2, but not CD11b or CD66b, was associated with a lower risk of relapse; CXCR2 remained significant in multivariate analysis. Our data suggest that CXCR2 is a stromal marker of TNBC. However, higher levels of CXCR2 predicted a lower risk of relapse.

Highlights

The implication of the tumor microenvironment has gained growing interest from the past years and it is well admitted that targeting tumor cells only could be insufficient to achieve optimal therapeutic responses
We have previously shown that the ligands of human chemokine receptor CXCR2 (CXCL1, CXCl2, CXCL3, CXCL5, CXCL6, CXCL7 and CXCL8) were coregulated in breast cancers, presumably because of their common location in a narrow region of chromosome 4q [12,13]
We reported that CXCR2, CD11b or CD66b expression was not correlated to the age of patients, the histological type, the size of the tumors, or lymph node status (Table 3)

Summary

Introduction

The implication of the tumor microenvironment has gained growing interest from the past years and it is well admitted that targeting tumor cells only could be insufficient to achieve optimal therapeutic responses. A variety of immune cells can be involved, including in particular, T lymphocytes, B lymphocytes, dendritic cells, macrophages, neutrophils and natural killers. These cells have the ability to establish contacts as well as distant interactions through the release of soluble factors. This will either favor or impair tumor growth, invasion and metastasis. One must emphasize that tumor cells are able to shape the stromal compartment though their physical or distant interactions with stromal cells, leading for instance to the acquisition of cancer associated fibroblast phenotype for fibroblasts or mesenchymal stem cells [3,4]

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