Boissière-Michot Florence, Jacot William, Massol Océane, Mollevi Caroline, Lazennec Gwendal
Institut Régional du Cancer de Montpellier (ICM), Val d'Aurelle, 34298 Montpellier, France.
Montpellier University, 34090 Montpellier, France.
Cancers (Basel). 2021 May 12;13(10):2328. doi: 10.3390/cancers13102328.
Chemokines and their receptors are key players in breast cancer progression and outcome. Previous studies have shown that the chemokine receptor CXCR2 was expressed at higher levels by cells of the tumor microenvironment in triple-negative breast cancers (TNBCs). The aim of this study was to focus our attention on a retrospective cohort of 290 TNBC cases and analyze the involvement of CXCR2, CD11b (a marker of granulocytes) and CD66b (a marker of neutrophils) and their link with immune infiltration and immune checkpoint markers. We report that high densities of CXCR2-, CD11b- and CD66b-positive cells were associated with high-grade tumors. Moreover, molecular apocrine TNBCs, defined here as tumors that express both AR and FOXA1 biomarkers, exhibited low levels of CXCR2 and CD11b. High CXCR2 and CD11b levels were correlated with elevated density of tumor-infiltrating lymphocytes (TILs), CD8+ cytotoxic lymphocytes, expression of PD-L1 by tumor and stromal cells and of PD-1 by stromal cells. On the other hand, CD66b levels were associated only with CD8+, stromal PD-L1 and PD-1 expression. In univariate analysis, low levels of CXCR2 were correlated with poor OS and RFS. In multivariate analysis, low levels of CXCR2 were associated with poor OS. Finally, in TNBC treated with adjuvant chemotherapy, CXCR2 density was associated with longer RFS. Overall, our data highlight the potential beneficial association of high levels of CXCR2 with a subgroup of TNBC patients characterized by a better prognosis.
趋化因子及其受体是乳腺癌进展和预后的关键因素。先前的研究表明，趋化因子受体CXCR2在三阴性乳腺癌（TNBC）的肿瘤微环境细胞中表达水平较高。本研究的目的是聚焦于290例TNBC病例的回顾性队列，分析CXCR2、CD11b（粒细胞标志物）和CD66b（中性粒细胞标志物）的参与情况及其与免疫浸润和免疫检查点标志物的联系。我们报告称，CXCR2、CD11b和CD66b阳性细胞的高密度与高级别肿瘤相关。此外，分子顶泌型TNBC（此处定义为同时表达AR和FOXA1生物标志物的肿瘤）表现出低水平的CXCR2和CD11b。高CXCR2和CD11b水平与肿瘤浸润淋巴细胞（TIL）、CD8 + 细胞毒性淋巴细胞的密度升高、肿瘤和基质细胞中PD-L1的表达以及基质细胞中PD-1的表达相关。另一方面，CD66b水平仅与CD8 +、基质PD-L1和PD-1表达相关。在单变量分析中，低水平的CXCR2与较差的总生存期（OS）和无复发生存期（RFS）相关。在多变量分析中，低水平的CXCR2与较差的OS相关。最后，在接受辅助化疗的TNBC中，CXCR2密度与更长的RFS相关。总体而言，我们的数据突出了高水平CXCR2与预后较好的TNBC患者亚组之间潜在有益关联。
