Department of Medical Oncology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, China.
Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Science and Medicine, University of Science and Technology of China, Hefei, China.
Front Immunol. 2023 Feb 6;14:1073550. doi: 10.3389/fimmu.2023.1073550. eCollection 2023.
Currently, targeting immune checkpoint molecules holds great promise for triple-negative breast cancer (TNBC). However, the expression landscape of immune checkpoint genes (ICGs) in TNBC remains largely unknown.
Herein, we systematically investigated the ICGs expression patterns in 422 TNBC samples. We evaluated the ICGs molecular typing based on the ICGs expression profile and explored the associations between ICGs molecular subtypes and tumor immune characteristics, clinical significance, and response to immune checkpoint inhibitors (ICIs).
Two ICGs clusters and two ICGs-related gene clusters were determined, which were involved in different survival outcomes, biological roles and infiltration levels of immune cells. We established a quantification system ICGs riskscore (named IRS) to assess the ICGs expression patterns for individuals. TNBC patients with lower IRS were characterized by increased immune cell infiltration, favorable clinical outcomes and high sensitivity to ICIs therapy. We also developed a nomogram model combining clinicopathological variables to predict overall survival in TNBC. Genomic feature analysis revealed that high IRS group presented an increased tumor mutation burden compared with the low IRS group.
Collectively, dissecting the ICGs expression patterns not only provides a new insight into TNBC subtypes but also deepens the understanding of ICGs in the tumor immune microenvironment.
目前，针对免疫检查点分子为三阴性乳腺癌（TNBC）带来了很大的希望。然而，TNBC 中免疫检查点基因（ICGs）的表达谱在很大程度上尚不清楚。
在此，我们系统地研究了 422 例 TNBC 样本中 ICGs 的表达模式。我们根据 ICGs 的表达谱评估了 ICGs 的分子分型，并探讨了 ICGs 分子亚型与肿瘤免疫特征、临床意义以及对免疫检查点抑制剂（ICIs）的反应之间的关联。
确定了两个 ICGs 簇和两个与 ICGs 相关的基因簇，它们涉及不同的生存结局、生物学作用和免疫细胞的浸润水平。我们建立了一个量化系统 ICGs 风险评分（命名为 IRS），用于评估个体的 ICGs 表达模式。IRS 较低的 TNBC 患者具有更高的免疫细胞浸润、更好的临床结局和对 ICIs 治疗的高敏感性。我们还开发了一个结合临床病理变量的列线图模型，用于预测 TNBC 的总生存期。基因组特征分析表明，高 IRS 组的肿瘤突变负担高于低 IRS 组。
总之，剖析 ICGs 的表达模式不仅为 TNBC 亚型提供了新的见解，而且加深了对肿瘤免疫微环境中 ICGs 的理解。
