Breast Cancer Biology, Comprehensive Cancer Centre, King's College London, Guy's Cancer Centre, Guy's Hospital, London, SE1 9RT, UK.
Translational Bioinformatics, Genomics Facility, National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, London, SE1 9RT, UK.
Commun Biol. 2020 Nov 4;3(1):644. doi: 10.1038/s42003-020-01359-5.
The tumour microenvironment plays a crucial role in the growth and progression of cancer, and the presence of tumour-associated macrophages (TAMs) is associated with poor prognosis. Recent studies have demonstrated that TAMs display transcriptomic, phenotypic, functional and geographical diversity. Here we show that a sialylated tumour-associated glycoform of the mucin MUC1, MUC1-ST, through the engagement of Siglec-9 can specifically and independently induce the differentiation of monocytes into TAMs with a unique phenotype that to the best of our knowledge has not previously been described. These TAMs can recruit and prolong the lifespan of neutrophils, inhibit the function of T cells, degrade basement membrane allowing for invasion, are inefficient at phagocytosis, and can induce plasma clotting. This macrophage phenotype is enriched in the stroma at the edge of breast cancer nests and their presence is associated with poor prognosis in breast cancer patients.
肿瘤微环境在癌症的生长和进展中起着至关重要的作用,肿瘤相关巨噬细胞(TAMs)的存在与预后不良有关。最近的研究表明,TAMs 表现出转录组、表型、功能和地理多样性。在这里,我们表明,一种唾液酸化的肿瘤相关糖型 MUC1 的粘蛋白 MUC1-ST 通过与 Siglec-9 的结合,可以特异性和独立地诱导单核细胞分化为具有独特表型的 TAMs,据我们所知,这种表型以前尚未被描述过。这些 TAMs 可以招募并延长中性粒细胞的寿命,抑制 T 细胞的功能,降解基底膜以允许侵袭,吞噬作用效率低下,并可诱导血浆凝固。这种巨噬细胞表型在乳腺癌巢边缘的基质中富集,其存在与乳腺癌患者的预后不良相关。