文章：

新兴趋化因子受体：肿瘤中CCR5或CXCR5的表达与局部晚期三阴性乳腺癌化疗反应差及预后不良相关

New Emerging Chemokine Receptors: CCR5 or CXCR5 on Tumor Is Associated with Poor Response to Chemotherapy and Poor Prognosis in Locally Advanced Triple-Negative Breast Cancer

原文发布日期：28 June 2024

DOI: 10.3390/cancers16132388

类型: Article

开放获取: 是

英文摘要：

Background: We aim to investigate any possible associations between chemokine receptor expression and responses to neoadjuvant chemotherapy (NAC) along with outcomes in patients with triple-negative breast cancer (TNBC) with locally advanced disease. Method: Expressions of chemokine receptors were examined immunohistochemically after staining archival tissue of surgical specimens (n = 63) using specific antibodies for CCR5, CCR7, CXCR4, and CXCR5. Results: Patients with high CCR5, CCR7, CXCR4, and CXCR5 expression on tumors and high CXCR4 expression on tumor-infiltrating lymphocytes (TILs) were less likely to have a pathological complete response (pCR) or Class 0-I RCB-Index compared to others. Patients with residual lymph node metastases (ypN-positive), high CCR5TM(tumor), and high CXCR4TMexpressions had an increased hazard ratio (HR) compared to others (DFS: HR = 2.655 [1.029–6.852]; DSS: HR = 2.763 [1.008–7.574]), (DFS: HR = 2.036 [0.805–5.148]; DSS: HR = 2.689 [1.020–7.090]), and (DFS: HR = 2.908 [1.080–7.829]; DSS: HR = 2.132 (0.778–5.846)), respectively. However, patients without CXCR5TILexpression had an increased HR compared to those with CXCR5TIL(DFS: 2.838 [1.266–6.362]; DSS: 4.211 [1.770–10.016]). Conclusions: High expression of CXCR4TMand CCR5TMwas found to be associated with poor prognosis, and CXCR5TMwas associated with poor chemotherapy response in the present cohort with locally advanced TNBC. Our results suggest that patients with TNBC could benefit from a chemokine receptor inhibitor therapy containing neoadjuvant chemotherapy protocols.

摘要翻译： 

背景：本研究旨在探讨趋化因子受体表达与局部晚期三阴性乳腺癌（TNBC）患者对新辅助化疗（NAC）的反应及预后之间的潜在关联。方法：采用针对CCR5、CCR7、CXCR4和CXCR5的特异性抗体，对手术标本存档组织（n=63）进行免疫组化染色，检测趋化因子受体的表达情况。结果：与表达水平较低的患者相比，肿瘤组织高表达CCR5、CCR7、CXCR4和CXCR5，以及肿瘤浸润淋巴细胞（TILs）高表达CXCR4的患者，获得病理完全缓解（pCR）或0-I级残留癌负荷指数（RCB-Index）的可能性较低。存在淋巴结残留转移（ypN阳性）、肿瘤组织高表达CCR5和高表达CXCR4的患者，其风险比（HR）均较其他患者升高（无病生存期[DFS]：HR=2.655[1.029–6.852]；疾病特异性生存期[DSS]：HR=2.763[1.008–7.574]）、（DFS：HR=2.036[0.805–5.148]；DSS：HR=2.689[1.020–7.090]）以及（DFS：HR=2.908[1.080–7.829]；DSS：HR=2.132[0.778–5.846]）。然而，与TILs表达CXCR5的患者相比，TILs不表达CXCR5的患者HR更高（DFS：2.838[1.266–6.362]；DSS：4.211[1.770–10.016]）。结论：在本局部晚期TNBC队列中，肿瘤组织高表达CXCR4和CCR5与不良预后相关，而肿瘤组织高表达CXCR5与较差的化疗反应相关。我们的研究结果表明，TNBC患者可能受益于包含新辅助化疗方案的趋化因子受体抑制剂治疗。

原文链接：

New Emerging Chemokine Receptors: CCR5 or CXCR5 on Tumor Is Associated with Poor Response to Chemotherapy and Poor Prognosis in Locally Advanced Triple-Negative Breast Cancer