吞噬作用
生物
免疫系统
转录组
肿瘤微环境
促炎细胞因子
癌症研究
巨噬细胞
肿瘤进展
炎症
细胞生物学
免疫学
癌症
基因表达
体外
基因
生物化学
遗传学
作者
Michael Gonzalez,Daniel Lu,Maryam Yousefi,Ashley V. Kroll,Chen Hao Lo,Carlos G. Briseño,J. E. V. Watson,Sergey V. Novitskiy,Vanessa Arias,Hong Zhou,Andres Plata Stapper,Min K. Tsai,Emily L. Ashkin,Christopher W. Murray,Chi-Ming Li,Monte M. Winslow,Kristin V. Tarbell
摘要
Phagocytosis is a key macrophage function, but how phagocytosis shapes tumor-associated macrophage (TAM) phenotypes and heterogeneity in solid tumors remains unclear. Here, we utilized both syngeneic and novel autochthonous lung tumor models in which neoplastic cells express the fluorophore tdTomato (tdTom) to identify TAMs that have phagocytosed neoplastic cells in vivo. Phagocytic tdTompos TAMs upregulated antigen presentation and anti-inflammatory proteins, but downregulated classic proinflammatory effectors compared to tdTomneg TAMs. Single-cell transcriptomic profiling identified TAM subset-specific and common gene expression changes associated with phagocytosis. We uncover a phagocytic signature that is predominated by oxidative phosphorylation (OXPHOS), ribosomal, and metabolic genes, and this signature correlates with worse clinical outcome in human lung cancer. Expression of OXPHOS proteins, mitochondrial content, and functional utilization of OXPHOS were increased in tdTompos TAMs. tdTompos tumor dendritic cells also display similar metabolic changes. Our identification of phagocytic TAMs as a distinct myeloid cell state links phagocytosis of neoplastic cells in vivo with OXPHOS and tumor-promoting phenotypes.
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