Affiliations
- 1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
- 2Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing, PR China.
- 3Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, PR China.
- 4Department of Economics, Business and Statistics, University of Palermo, Palermo, Italy.
- 5Tumor Immunology Unit, Department of Sciences for Health Promotion and Mother-Child Care “G. D’Alessandro”, University of Palermo, Palermo, Italy.
- 6Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore.
- 7Institut National de la Santé Et de la Recherche Medicale (INSERM) U1015, Equipe Labellisée-Ligue Nationale contre le Cancer, Villejuif, France.
- 8Université Paris-Saclay, Gustave Roussy, Villejuif, France.
- 9Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- 10Department of Biomedical Informatics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- 11Department of Haematology-Oncology, National University Health System, Singapore, Singapore.
- 12NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- 13Department of Pathology, Chi-Mei Medical Center, Tainan City, Taiwan, ROC.
- 14Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Singapore.
- 15Kindstar Global Precision Medicine Institute, Wuhan, PR China.
- 16Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
- 17Tumor Immunology Unit, Department of Sciences for Health Promotion and Mother-Child Care “G. D’Alessandro”, University of Palermo, Palermo, Italy. claudio.tripodo@unipa.it.
- 18Histopathology Unit, Institute of Molecular Oncology Foundation (IFOM) ETS – The AIRC Institute of Molecular Oncology, Milan, Italy. claudio.tripodo@unipa.it.
- 19Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore. csiadj@nus.edu.sg.
- 20Department of Haematology-Oncology, National University Health System, Singapore, Singapore. csiadj@nus.edu.sg.
- 21NUS Centre for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. csiadj@nus.edu.sg.
- 22Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. csiadj@nus.edu.sg.
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.
PMID: 38459052 DOI: 10.1038/s41467-024-46220-z