학술논문
Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma.
Document Type
article
Author
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; Jeyasekharan, Anand
Source
Nature Communications. 15(1)
Subject
Language
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.