Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma.
Cell Rep
; 42(8): 112879, 2023 08 29.
Article
in En
| MEDLINE
| ID: mdl-37537844
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∗0101 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Opsoclonus-Myoclonus Syndrome
/
Neuroblastoma
Type of study:
Prognostic_studies
Limits:
Child
/
Humans
Language:
En
Journal:
Cell Rep
Year:
2023
Document type:
Article