由于在病人中存活时间短、转移和复发风险高，针对三阴性乳腺癌（TNBC）的治疗是一个困难的领域。尽管参与了肿瘤入侵和转移，但跨膜糖蛋白间质细胞黏附分子1（ICAM1）在TNBC中的作用机制尚不清楚。我们研究了ICAM1在TNBC中的作用，重点关注其表达、细胞存活、突变和肿瘤免疫。然后，利用与ICAM1相关的共表达基因创建了一个风险评分模型。根据其风险评分，我们将病人分为高风险组和低风险组。在高风险组和低风险组中分析了免疫功能、药物敏感性差异和体细胞变异。我们使用CMap数据库预测潜在的药物。然后，将ICAM-1表达低的TNBC细胞与经过PMA处理的THP-1细胞和CD8 T细胞共培养。此外，在与CD8 T细胞共培养时，检测了ICAM-1表达低的TNBC细胞的PD-1和CTLA4的表达。ICAM1参与白细胞细胞粘附、活动和免疫激活。ICAM1低表达组的病人比ICAM1高表达组的病人具有较短的无病生存期（DFS）。ICAM1水平升高的组显示出明显增加的T细胞调节水平、自然杀伤细胞静息和M1巨噬细胞。ICAM1的表达与免疫检查点药物相关。风险评分模型的预后能力优于单个基因。高风险组的病人表现出较高的临床分期，M1巨噬细胞数量较多，并能更好地从免疫治疗中受益。高风险组的个体突变率显著升高，TP53、TTN和SYNE1基因突变率较高，同时TMB和PD-L1水平升高，TIDE得分降低。这些发现表明，免疫治疗可能对高风险组有利。此外，ICAM1低表达会促进M2巨噬细胞极化以及T细胞耗竭。总之，ICAM1低表达可能与免疫逃逸有关，导致治疗反应差和预后较差。版权所有 © 2023 周、徐、徐、孙和陈。

Treating triple-negative breast cancer (TNBC) is a difficult landscape owing to its short survival times and high risk of metastasis and recurrence among patients. Although involved in tumor invasion and metastasis, the mechanism of action of intercellular adhesion molecule 1 (ICAM1), a trans-membrane glycoprotein, in TNBC is ambiguous.We examined ICAM1's role in TNBC, focusing on its expression, cell survival, mutation, and tumor immunity. Then, a risk score model was created utilizing co-expressed genes associated with ICAM1. According to their respective risk scores, we divided patients into high- and low-risk groups. Immune function, drug susceptibility differences, and somatic variants were analyzed in the high-and low-risk groups. And we used the CMap database to predict potential medications. Then, TNBC cells with low expression of ICAM-1 were co-cultured with PMA-treated THP-1 cells and CD8 T cells. In addition, We detected the expression of PD-1 and CTLA4 of low ICAM-1 expressing TNBC cells when they were cocultured with CD8 T cells.ICAM1 was found to be involved in leukocyte cell adhesion, motility, and immune activation. Patients with low-ICAM1 group had shorter disease-free survival (DFS) than those with high-ICAM1 group. The group with elevated levels of ICAM1 exhibited significantly increased levels of T-cell regulation, quiescence in natural killer (NK) cells, and M1 macrophage. ICAM1 expression was correlated with immune checkpoint drugs. The prognostic ability of the risk score model was found to be superior to that of individual genes. Patients categorized as high-risk exhibited elevated clinical stages, showed higher M1 macrophage numbers, and were able to benefit better from immunotherapy. Individuals belonging to the high-risk group exhibit significantly elevated mutation rates in TP53, TTN, and SYNE1 genes, along with increased TMB and PD-L1 levels and decreased TIDE scores. These findings suggest that immunotherapy may be advantageous for the high-risk group. Furthermore, low expression of ICAM1 was found to promote polarization to M2 macrophages along with T-cell exhaustion.In conclusion, Low ICAM1 expression may be related to immune escape, leading to poor treatment response and a worse prognosis.Copyright © 2023 Zhou, Xu, Xu, Sun and Chen.