TY - JOUR
T1 - Spatially-resolved transcriptomics reveal macrophage heterogeneity and prognostic significance in diffuse large B-cell lymphoma
AU - Liu, Min
AU - Bertolazzi, Giorgio
AU - Sridhar, Shruti
AU - Lee, Rui Xue
AU - Jaynes, Patrick
AU - Mulder, Kevin
AU - Syn, Nicholas
AU - Hoppe, Michal Marek
AU - Fan, Shuangyi
AU - Peng, Yanfen
AU - Thng, Jocelyn
AU - Chua, Reiya
AU - Jayalakshmi,
AU - Batumalai, Yogeshini
AU - De Mel, Sanjay
AU - Poon, Limei
AU - Chan, Esther Hian Li
AU - Lee, Joanne
AU - Hue, Susan Swee Shan
AU - Chang, Sheng Tsung
AU - Chuang, Shih Sung
AU - Chandy, K. George
AU - Ye, Xiaofei
AU - Pan-Hammarström, Qiang
AU - Ginhoux, Florent
AU - Chee, Yen Lin
AU - Ng, Siok Bian
AU - Tripodo, Claudio
AU - Jeyasekharan, Anand D.
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12/1
Y1 - 2024/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85187165961&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-46220-z
DO - 10.1038/s41467-024-46220-z
M3 - Article
C2 - 38459052
AN - SCOPUS:85187165961
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2113
ER -