癌症
结直肠癌
巨噬细胞
生物
计算生物学
进化生物学
癌症研究
生物信息学
遗传学
体外
作者
Magdalena Matusiak,John W. Hickey,David G.P. van IJzendoorn,Guolan Lu,Łukasz Kidziński,Shirley Zhu,Deana R.C. Colburg,Bogdan A. Luca,Darci Phillips,Sky W. Brubaker,Gregory W. Charville,Jeanne Shen,Kyle M. Loh,Derick Okwan-Duodu,Garry P. Nolan,Aaron M. Newman,Robert B. West,Matt van de Rijn
出处
期刊:Cancer Discovery
[American Association for Cancer Research]
日期:2024-03-28
标识
DOI:10.1158/2159-8290.cd-23-1300
摘要
Abstract Tumor-associated macrophages are transcriptionally heterogeneous, but the spatial distribution and cell interactions that shape macrophage tissue roles remain poorly characterized. Here, we spatially resolve five distinct human macrophage populations in normal and malignant human breast and colon tissue and reveal their cellular associations. This spatial map reveals that distinct macrophage populations reside in spatially segregated micro-environmental niches with conserved cellular compositions that are repeated across healthy and diseased tissue. We show that IL4I1+ macrophages phagocytose dying cells in areas with high cell turnover and predict good outcome in colon cancer. In contrast, SPP1+ macrophages are enriched in hypoxic and necrotic tumor regions and portend worse outcome in colon cancer. A subset of FOLR2+ macrophages is embedded in plasma cell niches. NLRP3+ macrophages co-localize with neutrophils and activate an inflammasome in tumors. Our findings indicate that a limited number of unique human macrophage niches function as fundamental building blocks in tissue.
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