Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma
Summary: Neuroblastoma is a lethal childhood solid tumor of developing peripheral nerves. Two percent of children with neuroblastoma develop opsoclonus myoclonus ataxia syndrome (OMAS), a paraneoplastic disease characterized by cerebellar and brainstem-directed autoimmunity but typically with outsta...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723008902 |
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| author | Miriam I. Rosenberg Erez Greenstein Martin Buchkovich Ayelet Peres Eric Santoni-Rugiu Lei Yang Martin Mikl Zalman Vaksman David L. Gibbs Dan Reshef Amy Salovin Meredith S. Irwin Arlene Naranjo Igor Ulitsky Pedro A. de Alarcon Katherine K. Matthay Victor Weigman Gur Yaari Jessica A. Panzer Nir Friedman John M. Maris |
| author_facet | Miriam I. Rosenberg Erez Greenstein Martin Buchkovich Ayelet Peres Eric Santoni-Rugiu Lei Yang Martin Mikl Zalman Vaksman David L. Gibbs Dan Reshef Amy Salovin Meredith S. Irwin Arlene Naranjo Igor Ulitsky Pedro A. de Alarcon Katherine K. Matthay Victor Weigman Gur Yaari Jessica A. Panzer Nir Friedman John M. Maris |
| author_sort | Miriam I. Rosenberg |
| collection | DOAJ |
| description | Summary: Neuroblastoma is a lethal childhood solid tumor of developing peripheral nerves. Two percent of children with neuroblastoma develop opsoclonus myoclonus ataxia syndrome (OMAS), a paraneoplastic disease characterized by cerebellar and brainstem-directed autoimmunity but typically with outstanding cancer-related outcomes. We compared tumor transcriptomes and tumor-infiltrating T and B cell repertoires from 38 OMAS subjects with neuroblastoma to 26 non-OMAS-associated neuroblastomas. We found greater B and T cell infiltration in OMAS-associated tumors compared to controls and showed that both were polyclonal expansions. Tertiary lymphoid structures (TLSs) were enriched in OMAS-associated tumors. We identified significant enrichment of the major histocompatibility complex (MHC) class II allele HLA-DOB∗01:01 in OMAS patients. OMAS severity scores were associated with the expression of several candidate autoimmune genes. We propose a model in which polyclonal auto-reactive B lymphocytes act as antigen-presenting cells and drive TLS formation, thereby supporting both sustained polyclonal T cell-mediated anti-tumor immunity and paraneoplastic OMAS neuropathology. |
| first_indexed | 2024-03-12T11:53:24Z |
| format | Article |
| id | doaj.art-506516905d124cd99326d2bc5f05f4f1 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-12T11:53:24Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-506516905d124cd99326d2bc5f05f4f12023-08-31T05:02:01ZengElsevierCell Reports2211-12472023-08-01428112879Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastomaMiriam I. Rosenberg0Erez Greenstein1Martin Buchkovich2Ayelet Peres3Eric Santoni-Rugiu4Lei Yang5Martin Mikl6Zalman Vaksman7David L. Gibbs8Dan Reshef9Amy Salovin10Meredith S. Irwin11Arlene Naranjo12Igor Ulitsky13Pedro A. de Alarcon14Katherine K. Matthay15Victor Weigman16Gur Yaari17Jessica A. Panzer18Nir Friedman19John M. Maris20Hebrew University of Jerusalem, Edmond Safra Campus, Givat Ram, Jerusalem 91904, Israel; Corresponding authorDepartment of Immunology, Weizmann Institute of Science, Rehovot 7610001, IsraelQ2 Solutions, Durham, NC, USABio-engineering, Faculty of Engineering, Bar Ilan University, Ramat Gan, Israel; Bar Ilan Institute of Nanotechnologies and Advanced Materials, Bar Ilan University, Ramat Gan, IsraelDepartment of Pathology, Rigshospitalet, Copenhagen University Hospital and Department of Clinical Medicine, University of Copenhagen, 2100 Copenhagen, DenmarkPacific Northwest Research Institute, Seattle, WA 98122, USADepartment of Human Biology, Faculty of Natural Sciences, University of Haifa, Mount Carmel, Haifa 31905, IsraelNew York Genome Center, New York, NY 10013, USAInstitute for Systems Biology, 401 Terry Avenue N, Seattle, WA 98109, USADepartment of Immunology, Weizmann Institute of Science, Rehovot 7610001, IsraelDivision of Neurology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USADepartment of Pediatrics and Division of Hematology-Oncology, Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON M5G1X8, CanadaDepartment of Biostatistics, University of Florida, Children’s Oncology Group Statistics & Data Center, Gainesville, FL, USADepartment of Immunology & Regenerative Biology, Weizmann Institute of Science, Rehovot 7610001, IsraelDepartment of Pediatrics, Hematology/Oncology, University of Illinois College of Medicine Peoria, Peoria, IL 61605, USADepartment of Pediatrics, UCSF School of Medicine, San Francisco, CA 94143, USAQ2 Solutions, Durham, NC, USABio-engineering, Faculty of Engineering, Bar Ilan University, Ramat Gan, Israel; Bar Ilan Institute of Nanotechnologies and Advanced Materials, Bar Ilan University, Ramat Gan, IsraelDivision of Neurology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USADepartment of Immunology, Weizmann Institute of Science, Rehovot 7610001, IsraelDepartment of Pediatrics and Division of Oncology, Children’s Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Corresponding authorSummary: Neuroblastoma is a lethal childhood solid tumor of developing peripheral nerves. Two percent of children with neuroblastoma develop opsoclonus myoclonus ataxia syndrome (OMAS), a paraneoplastic disease characterized by cerebellar and brainstem-directed autoimmunity but typically with outstanding cancer-related outcomes. We compared tumor transcriptomes and tumor-infiltrating T and B cell repertoires from 38 OMAS subjects with neuroblastoma to 26 non-OMAS-associated neuroblastomas. We found greater B and T cell infiltration in OMAS-associated tumors compared to controls and showed that both were polyclonal expansions. Tertiary lymphoid structures (TLSs) were enriched in OMAS-associated tumors. We identified significant enrichment of the major histocompatibility complex (MHC) class II allele HLA-DOB∗01:01 in OMAS patients. OMAS severity scores were associated with the expression of several candidate autoimmune genes. We propose a model in which polyclonal auto-reactive B lymphocytes act as antigen-presenting cells and drive TLS formation, thereby supporting both sustained polyclonal T cell-mediated anti-tumor immunity and paraneoplastic OMAS neuropathology.http://www.sciencedirect.com/science/article/pii/S2211124723008902CP: CancerCP: Immunology |
| spellingShingle | Miriam I. Rosenberg Erez Greenstein Martin Buchkovich Ayelet Peres Eric Santoni-Rugiu Lei Yang Martin Mikl Zalman Vaksman David L. Gibbs Dan Reshef Amy Salovin Meredith S. Irwin Arlene Naranjo Igor Ulitsky Pedro A. de Alarcon Katherine K. Matthay Victor Weigman Gur Yaari Jessica A. Panzer Nir Friedman John M. Maris Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma Cell Reports CP: Cancer CP: Immunology |
| title | Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma |
| title_full | Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma |
| title_fullStr | Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma |
| title_full_unstemmed | Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma |
| title_short | Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma |
| title_sort | polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma |
| topic | CP: Cancer CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723008902 |
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