Thyroid and Breast Department III, Cangzhou Central Hospital, Cangzhou, Hebei Province, China.
Hebei Medical University, Shijiazhuang, Hebei Province, China.
PLoS One. 2023 Dec 21;18(12):e0293469. doi: 10.1371/journal.pone.0293469. eCollection 2023.
ICOS (Inducible T Cell Costimulator), one of the co-stimulatory B7 superfamily members, was characterized as a co-stimulatory receptor for T-cell enhancement. However, the role of ICOS in breast cancer remains largely unknown. The present study systematically investigated the expression pattern and its relation to clinical characteristics and immunotherapy by integrating multiple clinical cohorts and large-scale gene expression data. This study included 2994 breast tumor samples with transcriptome data and matched clinical data. To make our findings more reliable, we set the TCGA cohort as the discovery set and the METABRIC cohort as the validation set. The expression of ICOS in breast cancer is strongly associated with major clinical and molecular characteristics. There is an association between higher ICOS expression and malignant subtypes and grades of tumors. In addition, gene ontology analysis based on genes significantly correlated with ICOS expression indicated that the expression of ICOS is mainly associated with immune responses and inflammation. We also observed strong correlations between ICOS and other promising immune-checkpoint molecules, including PD1, PDL1, CTLA4, and IDO1. Furthermore, we found that ICOS expression is associated with the response to anti-PDL1 immunotherapy and may serve as a biomarker for immunotherapy prediction. Our results indicated higher ICOS expression is significantly associated with favorable survival in triple-negative breast cancer (TNBC) patients, but not for all subtypes of breast cancer patients. In summary, ICOS correlates with higher malignant breast cancers, and it contributes to the regulation of the immune microenvironment of breast tumors, making it a potential biomarker and immunotherapy target.
ICOS（诱导型 T 细胞共刺激因子）是 B7 共刺激因子超家族的成员之一，被认为是 T 细胞增强的共刺激受体。然而，ICOS 在乳腺癌中的作用在很大程度上尚不清楚。本研究通过整合多个临床队列和大规模基因表达数据，系统研究了 ICOS 的表达模式及其与临床特征和免疫治疗的关系。本研究纳入了 2994 例具有转录组数据和匹配临床数据的乳腺癌肿瘤样本。为了使我们的研究结果更加可靠，我们将 TCGA 队列作为发现集，METABRIC 队列作为验证集。ICOS 在乳腺癌中的表达与主要临床和分子特征密切相关。ICOS 表达较高与肿瘤的恶性亚型和分级有关。此外，基于与 ICOS 表达显著相关的基因进行基因本体分析表明，ICOS 的表达主要与免疫反应和炎症有关。我们还观察到 ICOS 与其他有前途的免疫检查点分子（包括 PD1、PDL1、CTLA4 和 IDO1）之间存在强烈的相关性。此外，我们发现 ICOS 表达与抗 PDL1 免疫治疗的反应相关，并且可能作为免疫治疗预测的生物标志物。我们的研究结果表明，在三阴性乳腺癌（TNBC）患者中，ICOS 表达水平较高与生存情况较好显著相关，但对所有乳腺癌亚型患者并非如此。综上所述，ICOS 与恶性程度较高的乳腺癌相关，并且有助于调节乳腺癌肿瘤的免疫微环境，使其成为潜在的生物标志物和免疫治疗靶点。
