Recently, immune checkpoint inhibitors (ICIs) have been successfully used for treating melanoma. Unfortunately, many breast cancer (BC) patients show low response to ICIs due to the lack of infiltrating immune cells. Previous studies revealed that chemokine-CXC receptors (CXCRs) play a crucial role in leukocyte infiltration and promote cancer cell proliferation, migration, metastasis, and angiogenesis. However, the underlying functions of CXCRs in cancer-immunity cycle remain unclear. In this study, we firstly found that in comparison to normal tissues, BC tissues, especially basal-like BC, showed increased mRNA levels of CXCR3/4/5/6/8, but decreased CXCR1/2/7 expression using UALCAN and TIMER database. Interestingly, it’s was found that the mRNA levels of CXCR3/4/5/6 were decreased in lymphocyte depleted of the BC immune subtype. Subsequently, functional enrichment analysis of distinct CXCRs indicated that CXCR3/4/5/6 were strongly associated to immune-related biological functions. Therefore, further analysis using TIMER and TISIDB database suggested that CXCR3/4/5/6 expression were strongly correlated with tumor-infiltrating lymphocytes (TILs) and immune checkpoints in BC. Finally, Kaplan–Meier Plotter analysis indicated that high mRNA expression of CXCR4 predicted worse relapse-free survival (RFS), whereas CXCR3/5/6 indicated better RFS in BC patients. These findings suggest a therapeutic value for CXCR3/4/5/6 in combination with ICIs for the treatment of BC.

最近，免疫检查点抑制剂（ICIs）已成功用于治疗黑色素瘤。不幸的是，由于缺乏浸润性免疫细胞，许多乳腺癌（BC）患者显示出对ICI的低响应。先前的研究表明，趋化因子CXC受体（CXCR）在白细胞浸润中起关键作用，并促进癌细胞的增殖，迁移，转移和血管生成。然而，CXCRs在癌症-免疫周期中的潜在功能仍不清楚。在这项研究中，我们首先发现与正常组织相比，BC组织，特别是基底样BC，使用UALCAN和TIMER表达的CXCR3 / 4/5/6/8 mRNA表达水平升高，但CXCR1 / 2/7表达降低数据库。有趣的是，发现在BC免疫亚型缺失的淋巴细胞中CXCR3 / 4/5/6的mRNA水平降低了。后来，不同CXCR的功能富集分析表明CXCR3 / 4/5/6与免疫相关的生物学功能密切相关。因此，使用TIMER和TISIDB数据库进行的进一步分析表明，CXCR3 / 4/5/6表达与BC中的肿瘤浸润淋巴细胞（TIL）和免疫检查点密切相关。最后，Kaplan–Meier绘图仪分析表明CXCR4的高mRNA表达预示着更差的无复发生存期（RFS），而CXCR3 / 5/6表明BC患者的RFS更好。这些发现表明CXCR3 / 4/5/6与ICIs联合用于治疗BC的治疗价值。使用TIMER和TISIDB数据库进行的进一步分析表明，CXCR3 / 4/5/6表达与BC中的肿瘤浸润淋巴细胞（TIL）和免疫检查点密切相关。最后，Kaplan–Meier绘图仪分析表明CXCR4的高mRNA表达预示着更差的无复发生存期（RFS），而CXCR3 / 5/6表明BC患者的RFS更好。这些发现表明CXCR3 / 4/5/6与ICIs联合用于治疗BC的治疗价值。使用TIMER和TISIDB数据库进行的进一步分析表明，CXCR3 / 4/5/6表达与BC中的肿瘤浸润淋巴细胞（TIL）和免疫检查点密切相关。最后，Kaplan–Meier绘图仪分析表明CXCR4的高mRNA表达预示着更差的无复发生存期（RFS），而CXCR3 / 5/6表明BC患者的RFS更好。这些发现表明CXCR3 / 4/5/6与ICIs联合用于治疗BC的治疗价值。