Nature communications · 2024
Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma.
СтатьяПоддержка исследования: вне правительства СШАResearch Support, N.I.H., IntramuralНазвание и аннотация: Перевод пока не подготовлен
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Liu Min, Bertolazzi Giorgio, Sridhar Shruti, Lee Rui Xue, Jaynes Patrick, Mulder Kevin, Syn Nicholas, Hoppe Michal Marek, Fan Shuangyi, Peng Yanfen, Thng Jocelyn, Chua Reiya, Jayalakshmi, Batumalai Yogeshini, De Mel Sanjay, Poon Limei, Chan Esther Hian Li, Lee Joanne, Hue Susan Swee-Shan, Chang Sheng-Tsung, Chuang Shih-Sung, Chandy K George, Ye Xiaofei, Pan-Hammarström Qiang, Ginhoux Florent, Chee Yen Lin, Ng Siok-Bian, Tripodo Claudio, Jeyasekharan Anand D
Аннотация
Macrophages are abundant immune cells in the microenvironment of diffuse large B-cell lymphoma (DLBCL). Macrophage estimation by immunohistochemistry shows varying prognostic significance across studies in DLBCL, and does not provide a comprehensive analysis of macrophage subtypes. Here, using digital spatial profiling with whole transcriptome analysis of CD68+ cells, we characterize macrophages in distinct spatial niches of reactive lymphoid tissues (RLTs) and DLBCL. We reveal transcriptomic differences between macrophages within RLTs (light zone /dark zone, germinal center/ interfollicular), and between disease states (RLTs/ DLBCL), which we then use to generate six spatially-derived macrophage signatures (MacroSigs). We proceed to interrogate these MacroSigs in macrophage and DLBCL single-cell RNA-sequencing datasets, and in gene-expression data from multiple DLBCL cohorts. We show that specific MacroSigs are associated with cell-of-origin subtypes and overall survival in DLBCL. This study provides a spatially-resolved whole-transcriptome atlas of macrophages in reactive and malignant lymphoid tissues, showing biological and clinical significance.