已经确认，肿瘤免疫微环境（TIME）在决定乳腺癌（BrCa）的治疗反应和临床结果方面起关键作用。因此，鉴定TIME的特征对于指导治疗和预后评估至关重要。通过单细胞RNA测序（scRNA-seq）研究发现，BrCa中TIME的细胞组成具有异质性。从肿瘤区富集亚型和免疫浸润亚型中分别提取了上调基因CRABP2和CD69，建立了基于CRABP2和CD69表达的CRABP2/CD69特征，并在多个队列中验证了其对临床结果和新辅助化疗（NAT）反应的预测价值。此外，还探讨了CRABP2在BrCa细胞中的致癌作用。 基于BrCa中TIME的异质性细胞组成，将BrCa样本分为肿瘤区富集亚型和免疫浸润亚型，两者均具有明显不同的预后和化疗反应。接下来，我们提取了CRABP2作为肿瘤区富集亚型的生物标志物，提取了CD69作为免疫浸润亚型的生物标志物。基于CRABP2/CD69特征，将BrCa样本重新分为三个亚型，其中CRABP2高CD69低亚型预后最差，化疗反应最低，而CRABP2低CD69高亚型则呈相反结果。此外，CARBP2在BrCa中具有新的致癌基因功能，促进肿瘤细胞的增殖、迁移和侵袭，并且CRABP2的抑制会激活细胞毒性T淋巴细胞（CTL）。 CRABP2/CD69特征与TIME的特征显著相关，并且能有效预测临床结果。此外，确定CRABP2是一种新的致癌基因，可以成为乳腺癌的治疗靶点。 © 2023. 作者，授权给斯普林格自然出版集团有限公司独家使用。

It has been acknowledged that the tumour immune microenvironment (TIME) plays a critical role in determining therapeutic responses and clinical outcomes in breast cancer (BrCa). Thus, the identification of the TIME features is essential for guiding therapy and prognostic assessment for BrCa.The heterogeneous cellular composition of the TIME in BrCa by single-cell RNA sequencing (scRNA-seq). Two subtype-special genes upregulated in the tumour-rich subtype and the immune-infiltrating subtype were extracted, respectively. The CRABP2/CD69 signature was established based on CRABP2 and CD69 expression, and its predictive values for the clinical outcome and the neoadjuvant chemotherapy (NAT) responses were validated in multiple cohorts. Moreover, the oncogenic role of CRABP2 was explored in BrCa cells.Based on the heterogeneous cellular composition of the TIME in BrCa, the BrCa samples could be divided into the tumour-rich subtype and the immune-infiltrating subtype, which exhibited distinct prognosis and chemotherapeutic responses. Next, we extracted CRABP2 as the biomarker for the tumour-rich subtype and CD69 as the biomarker for the immune-infiltrating subtype. Based on the CRABP2/CD69 signature, BrCa samples were re-divided into three subtypes, and the CRABP2highCD69low subtype exhibited the worst prognosis and the lowest chemotherapeutic response, while the CRABP2lowCD69high subtype showed the opposite results. Furthermore, CARBP2 functioned as a novel oncogene in BrCa, which promoted tumour cell proliferation, migration, and invasion, and CRABP2 inhibition triggered the activation of cytotoxic T lymphocytes (CTLs).The CRABP2/CD69 signature is significantly associated with the TIME features and could effectively predict the clinical outcome. Also, CRABP2 is determined to be a novel oncogene, which could be a therapeutic target in BrCa.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.