共刺激分子被认为是当前可用免疫疗法的新靶点或潜在补充，但其在三阴性乳腺癌 (TNBC) 中的表达模式和临床价值尚待阐明。TNBC 患者的基因表达谱数据集来自癌症基因组图谱和基因表达综合数据库。使用最小绝对收缩和选择算子 (LASSO) 和支持向量机递归特征消除 (SVM-RFE) 算法来识别用于分层个体化肿瘤免疫微环境 (TIME) 的诊断生物标志物。此外，我们通过多重免疫组织化学（mIHC）探讨了它们与免疫治疗反应的关联。总共获得了 60 个共刺激分子基因（CMG），并通过 K 确定了两个不同的 TIME 亚类（“热”和“冷”）。 -表示聚类方法。 “热”肿瘤呈现出更高的活化免疫细胞浸润，即 CD4 记忆激活 T 细胞、静息 NK 细胞、M1 巨噬细胞和 CD8 T 细胞，从而富集 B 细胞和 T 细胞受体信号通路。 LASSO 和 SVM-RFE 算法确定了三种 CMG（CD86、TNFRSF17 和 TNFRSF1B）作为诊断生物标志物。接下来，构建了一种新的诊断列线图来预测个体化 TIME 状态，并在 TCGA、GSE76250 和 GSE58812 数据库中验证了良好的预测准确性。进一步的 mIHC 证实，CD86、TNFRSF17 和 TNFRSF1B 水平较高的 TNBC 患者往往对免疫治疗有反应。这项研究补充了有关 CMG 在 TNBC 中价值的证据。此外，CD86、TNFRSF17和TNFRSF1B被发现是潜在的生物标志物，显着促进TNBC患者选择免疫治疗指导。版权所有©2024张，翟，马，吴，蔡，黄，周和段。

Costimulatory molecules are putative novel targets or potential additions to current available immunotherapy, but their expression patterns and clinical value in triple-negative breast cancer (TNBC) are to be clarified.The gene expression profiles datasets of TNBC patients were obtained from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Diagnostic biomarkers for stratifying individualized tumor immune microenvironment (TIME) were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) algorithms. Additionally, we explored their associations with response to immunotherapy via the multiplex immunohistochemistry (mIHC).A total of 60 costimulatory molecule genes (CMGs) were obtained, and we determined two different TIME subclasses ("hot" and "cold") through the K-means clustering method. The "hot" tumors presented a higher infiltration of activated immune cells, i.e., CD4 memory-activated T cells, resting NK cells, M1 macrophages, and CD8 T cells, thereby enriched in the B cell and T cell receptor signaling pathways. LASSO and SVM-RFE algorithms identified three CMGs (CD86, TNFRSF17 and TNFRSF1B) as diagnostic biomarkers. Following, a novel diagnostic nomogram was constructed for predicting individualized TIME status and was validated with good predictive accuracy in TCGA, GSE76250 and GSE58812 databases. Further mIHC conformed that TNBC patients with high CD86, TNFRSF17 and TNFRSF1B levels tended to respond to immunotherapy.This study supplemented evidence about the value of CMGs in TNBC. In addition, CD86, TNFRSF17 and TNFRSF1B were found as potential biomarkers, significantly promoting TNBC patient selection for immunotherapeutic guidance.Copyright © 2024 Zhang, Zhai, Ma, Wu, Cai, Huang, Zhou and Duan.