乳腺癌分为激素受体阳性 (HR )、HER2 阳性 (HER2 ) 和三阴性 (TNBC) 亚型，根据肿瘤浸润淋巴细胞 (TIL) 的数量表现出不同的结果。为了探索 TIL 水平在不同亚型中的不同作用，我们对 31 名乳腺癌患者进行了单细胞 RNA 测序。具有高 TIL 水平（TIL-high）的 HR 乳腺癌显示 SPP1 巨噬细胞增加，其他单核细胞/巨噬细胞（单/宏）亚群中 SPP1 表达增加，以及与单/宏中细胞外基质（ECM）重塑相关的通路丰富。此外，细胞间相互作用分析显示，在 TIL 高 HR 乳腺癌中，SPP1 巨噬细胞和 T 细胞之间的相互作用中 SPP1、MIF 和 FN1 信号传导增强。空间转录组学数据强调了 TIL 高 HR 乳腺癌中 SPP1 巨噬细胞、CD8 T 细胞和 CD4 T 细胞的紧密接近。我们的研究结果揭示了 SPP1 巨噬细胞对 TIL 高 HR 乳腺癌中 T 细胞的新影响，可能解释不良预后并为针对性干预提供见解。© 2024。作者。

Breast cancer categorized into hormone receptor-positive (HR+), HER2-positive (HER2+), and triple-negative (TNBC) subtypes, exhibits varied outcomes based on the number of tumor-infiltrating lymphocytes (TILs). To explore the divergent roles of TIL levels across different subtypes, we employed single-cell RNA sequencing on 31 patients with breast cancer. HR+ breast cancer with high TIL levels (TIL-high) revealed increased SPP1+ macrophages, increased SPP1 expression in other monocytes/macrophages (mono/macro) subgroups, and enriched pathways associated with extracellular matrix (ECM) remodeling in mono/macro. Moreover, cell-cell interaction analyses revealed enhanced SPP1, MIF, and FN1 signaling in the interaction between SPP1+ macrophages and T-cells in TIL-high HR+ breast cancer. Spatial transcriptomics data highlighted the close proximity of SPP1+ macrophages, CD8+ T-cells, and CD4+ T-cells in TIL-high HR+ breast cancer. Our findings unveil the novel influence of SPP1+ macrophages on T-cells in TIL-high HR+ breast cancer, potentially explaining the poor prognosis and offering insights for targeted interventions.© 2024. The Author(s).