Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma.
Publication Title
Cell Rep
Document Type
Article
Publication Date
8-29-2023
Keywords
Child; Humans; Autoimmunity; Neuroblastoma; Opsoclonus-Myoclonus Syndrome; Autoantibodies; Genes, MHC Class II; Ataxia; CP: Cancer; CP: Immunology; IgH; TCRB; ataxia; autoimmunity; immune profiling; myoclonus; neuroblastoma; opsoclonus; paraneoplastic; repertoires; washington; isb
Abstract
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
Clinical Institute
Neurosciences (Brain & Spine)
Clinical Institute
Cancer
Clinical Institute
Women & Children
Specialty/Research Institute
Neurosciences
Specialty/Research Institute
Oncology
DOI
10.1016/j.celrep.2023.112879
