Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma

• Main Authors: 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, Kanianthara George, Ye, Xiaofei, Pan-Hammarström, Qiang, Ginhoux, Florent, Chee, Yen Lin, Ng, Siok-Bian, Tripodo, Claudio, Jeyasekharan, Anand D.
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2024
• Subjects: Medicine, Health and Life Sciences; Cancer prognosis; Cell heterogeneity
• Online Access: https://hdl.handle.net/10356/174908
• Institution: Nanyang Technological University

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.