1. Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma.
- Author
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Liu, Min, Bertolazzi, Giorgio, Sridhar, Shruti, Lee, Rui, Jaynes, Patrick, Mulder, Kevin, Syn, Nicholas, Hoppe, Michal, Fan, Shuangyi, Peng, Yanfen, Thng, Jocelyn, Chua, Reiya, Batumalai, Yogeshini, De Mel, Sanjay, Poon, Limei, Chan, Esther, Lee, Joanne, Hue, Susan, Chang, Sheng-Tsung, Chuang, Shih-Sung, Chandy, K, Ye, Xiaofei, Pan-Hammarström, Qiang, Ginhoux, Florent, Chee, Yen, Ng, Siok-Bian, Tripodo, Claudio, and Jeyasekharan, Anand
- Subjects
Humans ,Prognosis ,Lymphoma ,Large B-Cell ,Diffuse ,Gene Expression Profiling ,Transcriptome ,Germinal Center ,Tumor Microenvironment - Abstract
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.
- Published
- 2024