Breast cancer is the most commonly diagnosed cancer in women, with distant metastasis being the main cause of breast cancer-related deaths. Elucidating the changes in the tumor and immune ecosystems that are associated with metastatic disease is essential to improve understanding and ultimately treatment of metastasis. Here, we developed an in-depth, spatially resolved single-cell atlas of the phenotypic diversity of tumor and immune cells in primary human breast tumors and matched distant metastases, using imaging mass cytometry to analyze a total of 75 unique antibody targets. While the same tumor cell phenotypes were typically present in primary tumors and metastatic sites, suggesting a strong founder effect of the primary tumor, their proportions varied between matched samples. Notably, the metastatic site did not influence tumor phenotype composition, except for the brain. Metastatic sites exhibited a lower number of immune cells overall, but had a higher proportion of myeloid cells as well as exhausted and cytotoxic T cells. Myeloid cells showed distinct tissue-specific compositional signatures and increased presence of potentially matrix remodeling phenotypes in metastatic sites. This analysis of tumor and immune cell phenotypic composition of metastatic breast cancer highlights the heterogeneity of the disease within patients and across distant metastatic sites, indicating myeloid cells as the predominant immune modulators that could potentially be targeted at these sites.

中文翻译：

---

乳腺癌的远处转移在癌细胞组成上与原发性肿瘤相似，但在免疫细胞表型上有所不同


乳腺癌是女性中最常被诊断出的癌症，远处转移是乳腺癌相关死亡的主要原因。阐明与转移性疾病相关的肿瘤和免疫生态系统的变化对于提高对转移的理解并最终治疗至关重要。在这里，我们开发了一个深入的、空间分辨的单细胞图谱，展示了原发性人类乳腺肿瘤和匹配的远处转移中肿瘤和免疫细胞的表型多样性，使用成像质谱流式细胞术分析了总共 75 个独特的抗体靶标。虽然相同的肿瘤细胞表型通常存在于原发肿瘤和转移部位，表明原发肿瘤具有很强的创始人效应，但它们的比例在匹配样本之间有所不同。值得注意的是，转移部位不影响肿瘤表型组成，除了大脑。转移部位总体上表现出较少的免疫细胞数量，但骨髓细胞以及耗竭和细胞毒性 T 细胞的比例较高。髓系细胞显示出独特的组织特异性组成特征，并且转移部位潜在基质重塑表型的存在增加。这项对转移性乳腺癌的肿瘤和免疫细胞表型组成的分析强调了患者内部和远处转移部位疾病的异质性，表明骨髓细胞是可能靶向这些部位的主要免疫调节剂。