Title

Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma.

Document Type

Article

Publication Date

8-29-2023

Publication Title

Cell Rep

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∗01:01 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.

Clinical Institute

Neurosciences (Brain & Spine)

Clinical Institute

Cancer

Clinical Institute

Women & Children

Department

Neurosciences

Department

Oncology

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