Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota, Minneapolis, Minnesota, USA.
Molecular Pharmacology and Therapeutics Graduate Program, University of Minnesota, Minneapolis, Minnesota, USA.
Cancer Med. 2024 Feb;13(3):e7053. doi: 10.1002/cam4.7053.
Macrophages are innate immune cells that are associated with extensive phenotypic and functional plasticity and contribute to normal development, tissue homeostasis, and diseases such as cancer. In this review, we discuss the heterogeneity of tissue resident macrophages in the normal mammary gland and tumor-associated macrophages in breast cancer. Tissue resident macrophages are required for mammary gland development, where they have been implicated in promoting extracellular matrix remodeling, apoptotic clearance, and cellular crosstalk. In the context of cancer, tumor-associated macrophages are key drivers of growth and metastasis via their ability to promote matrix remodeling, angiogenesis, lymphangiogenesis, and immunosuppression.
We identified and summarized studies in Pubmed that describe the phenotypic and functional heterogeneity of macrophages and the implications of targeting individual subsets, specifically in the context of mammary gland development and breast cancer. We also identified and summarized recent studies using single-cell RNA sequencing to identify and describe macrophage subsets in human breast cancer samples.
Advances in single-cell RNA sequencing technologies have yielded nuances in macrophage heterogeneity, with numerous macrophage subsets identified in both the normal mammary gland and breast cancer tissue. Macrophage subsets contribute to mammary gland development and breast cancer progression in differing ways, and emerging studies highlight a role for spatial localization in modulating their phenotype and function.
Understanding macrophage heterogeneity and the unique functions of each subset in both normal mammary gland development and breast cancer progression may lead to more promising targets for the treatment of breast cancer.
巨噬细胞是先天免疫细胞，具有广泛的表型和功能可塑性，参与正常发育、组织稳态以及癌症等疾病的发生。在本篇综述中，我们讨论了正常乳腺组织中的驻留巨噬细胞和乳腺癌中的肿瘤相关巨噬细胞的异质性。组织驻留巨噬细胞对于乳腺发育是必需的，它们在促进细胞外基质重塑、细胞凋亡清除和细胞间通讯方面发挥作用。在癌症的背景下，肿瘤相关巨噬细胞通过促进基质重塑、血管生成、淋巴管生成和免疫抑制，成为肿瘤生长和转移的关键驱动因素。
我们在 Pubmed 数据库中识别并总结了描述巨噬细胞表型和功能异质性的研究，以及靶向特定亚群的意义，特别是在乳腺发育和乳腺癌的背景下。我们还识别并总结了最近使用单细胞 RNA 测序来鉴定和描述人类乳腺癌样本中巨噬细胞亚群的研究。
单细胞 RNA 测序技术的进步揭示了巨噬细胞异质性的细微差别，在正常乳腺和乳腺癌组织中都鉴定出了许多巨噬细胞亚群。巨噬细胞亚群以不同的方式促进乳腺发育和乳腺癌的进展，新出现的研究强调了空间定位在调节其表型和功能方面的作用。
了解巨噬细胞异质性以及每个亚群在正常乳腺发育和乳腺癌进展中的独特功能，可能为乳腺癌的治疗提供更有前途的靶点。
