Single-cell and spatial characterization of plasmablast-like lymphoma cells in primary central nervous system lymphoma
Abstract: Primary central nervous system lymphoma (PCNSL) is a rare, aggressive type of lymphoma, most often histologically diagnosed as diffuse large B-cell lymphoma (DLBCL). Recent advancements in single-cell sequencing have elucidated that the diverse germinal center states in systemic DLBCL mani...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Blood Neoplasia |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S295032802400058X |
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| author | Hiroki Kobayashi Ryota Chijimatsu Yusuke Naoi Yoshihiro Otani Ryo Mizuta Kentaro Fujii Joji Ishida Hiroyuki Murakami Hideki Ujiie Kazuhiro Ikeuchi Tomohiro Urata Keisuke Seike Hideaki Fujiwara Noboru Asada Nobuharu Fujii Ken-ichi Matsuoka Yasuharu Sato Yoshinobu Maeda Daisuke Ennishi |
| author_facet | Hiroki Kobayashi Ryota Chijimatsu Yusuke Naoi Yoshihiro Otani Ryo Mizuta Kentaro Fujii Joji Ishida Hiroyuki Murakami Hideki Ujiie Kazuhiro Ikeuchi Tomohiro Urata Keisuke Seike Hideaki Fujiwara Noboru Asada Nobuharu Fujii Ken-ichi Matsuoka Yasuharu Sato Yoshinobu Maeda Daisuke Ennishi |
| author_sort | Hiroki Kobayashi |
| collection | DOAJ |
| description | Abstract: Primary central nervous system lymphoma (PCNSL) is a rare, aggressive type of lymphoma, most often histologically diagnosed as diffuse large B-cell lymphoma (DLBCL). Recent advancements in single-cell sequencing have elucidated that the diverse germinal center states in systemic DLBCL manifest as tumor cell diversity, intricately linked to variations in the microenvironment. However, detailed characterization of intratumoral heterogeneity reflecting B-cell states in PCNSL remains elusive. Here, we conducted single-cell and spatial multiomic analyses to elucidate the cellular and spatial heterogeneity and the microenvironment in PCNSL. We identified a distinctive lymphoma subpopulation with gene and protein expression similar to that of plasmablasts (PBLs), enriched in some patients with PCNSL. B-cell receptor (BCR) analysis revealed that BCR clonotypes of the PBL signature subpopulation were shared with other subpopulations, suggesting a common origin with other lymphoma cell subtypes. Spatial analysis additionally revealed several localization patterns of PBL signature subpopulations within the tissue, indicating spatial heterogeneity. An expansion study showed that ∼40% of patients with PCNSL had a PBL signature subpopulation, as defined by CD138 immunohistochemistry staining. Additionally, patients with a PBL signature subpopulation and low CD3+ cell infiltration exhibited a worse prognosis. Finally, intercellular communication analysis suggested that the PBL signature subpopulation had distinct cellular interactions with the microenvironment. In summary, our study identified a tumor subpopulation with a PBL signature in PCNSL, suggesting distinct molecular and spatial cross talk with the microenvironment. These findings provided new insights into the biological mechanisms of PCNSL. |
| format | Article |
| id | doaj-art-947b2c860fea418c8e59b4257dab2006 |
| institution | Kabale University |
| issn | 2950-3280 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Neoplasia |
| spelling | doaj-art-947b2c860fea418c8e59b4257dab20062025-01-12T05:26:24ZengElsevierBlood Neoplasia2950-32802025-02-0121100058Single-cell and spatial characterization of plasmablast-like lymphoma cells in primary central nervous system lymphomaHiroki Kobayashi0Ryota Chijimatsu1Yusuke Naoi2Yoshihiro Otani3Ryo Mizuta4Kentaro Fujii5Joji Ishida6Hiroyuki Murakami7Hideki Ujiie8Kazuhiro Ikeuchi9Tomohiro Urata10Keisuke Seike11Hideaki Fujiwara12Noboru Asada13Nobuharu Fujii14Ken-ichi Matsuoka15Yasuharu Sato16Yoshinobu Maeda17Daisuke Ennishi18Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanCenter for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, JapanDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; Center for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, JapanDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanDepartment of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanDepartment of Molecular Hematopathology, Okayama University Graduate School of Health Sciences, Okayama, JapanDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanDepartment of Hematology and Oncology, Okayama University Hospital, Okayama, JapanDepartment of Hematology and Oncology, Okayama University Hospital, Okayama, JapanDepartment of Hematology and Oncology, Okayama University Hospital, Okayama, JapanDivision of Blood Transfusion, Okayama University Hospital, Okayama, JapanDepartment of Hematology and Oncology, Okayama University Hospital, Okayama, JapanDepartment of Molecular Hematopathology, Okayama University Graduate School of Health Sciences, Okayama, JapanDepartment of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, JapanCenter for Comprehensive Genomic Medicine, Okayama University Hospital, Okayama, Japan; Correspondence: Daisuke Ennishi, Center for Comprehensive Genomic Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku Okayama City, Okayama 700-8558, Japan;Abstract: Primary central nervous system lymphoma (PCNSL) is a rare, aggressive type of lymphoma, most often histologically diagnosed as diffuse large B-cell lymphoma (DLBCL). Recent advancements in single-cell sequencing have elucidated that the diverse germinal center states in systemic DLBCL manifest as tumor cell diversity, intricately linked to variations in the microenvironment. However, detailed characterization of intratumoral heterogeneity reflecting B-cell states in PCNSL remains elusive. Here, we conducted single-cell and spatial multiomic analyses to elucidate the cellular and spatial heterogeneity and the microenvironment in PCNSL. We identified a distinctive lymphoma subpopulation with gene and protein expression similar to that of plasmablasts (PBLs), enriched in some patients with PCNSL. B-cell receptor (BCR) analysis revealed that BCR clonotypes of the PBL signature subpopulation were shared with other subpopulations, suggesting a common origin with other lymphoma cell subtypes. Spatial analysis additionally revealed several localization patterns of PBL signature subpopulations within the tissue, indicating spatial heterogeneity. An expansion study showed that ∼40% of patients with PCNSL had a PBL signature subpopulation, as defined by CD138 immunohistochemistry staining. Additionally, patients with a PBL signature subpopulation and low CD3+ cell infiltration exhibited a worse prognosis. Finally, intercellular communication analysis suggested that the PBL signature subpopulation had distinct cellular interactions with the microenvironment. In summary, our study identified a tumor subpopulation with a PBL signature in PCNSL, suggesting distinct molecular and spatial cross talk with the microenvironment. These findings provided new insights into the biological mechanisms of PCNSL.http://www.sciencedirect.com/science/article/pii/S295032802400058X |
| spellingShingle | Hiroki Kobayashi Ryota Chijimatsu Yusuke Naoi Yoshihiro Otani Ryo Mizuta Kentaro Fujii Joji Ishida Hiroyuki Murakami Hideki Ujiie Kazuhiro Ikeuchi Tomohiro Urata Keisuke Seike Hideaki Fujiwara Noboru Asada Nobuharu Fujii Ken-ichi Matsuoka Yasuharu Sato Yoshinobu Maeda Daisuke Ennishi Single-cell and spatial characterization of plasmablast-like lymphoma cells in primary central nervous system lymphoma Blood Neoplasia |
| title | Single-cell and spatial characterization of plasmablast-like lymphoma cells in primary central nervous system lymphoma |
| title_full | Single-cell and spatial characterization of plasmablast-like lymphoma cells in primary central nervous system lymphoma |
| title_fullStr | Single-cell and spatial characterization of plasmablast-like lymphoma cells in primary central nervous system lymphoma |
| title_full_unstemmed | Single-cell and spatial characterization of plasmablast-like lymphoma cells in primary central nervous system lymphoma |
| title_short | Single-cell and spatial characterization of plasmablast-like lymphoma cells in primary central nervous system lymphoma |
| title_sort | single cell and spatial characterization of plasmablast like lymphoma cells in primary central nervous system lymphoma |
| url | http://www.sciencedirect.com/science/article/pii/S295032802400058X |
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