Q² Solutions

Polyclonal lymphoid expansion drives paraneoplastic autoimmunity in neuroblastoma

Cell Reports article, with contributions from Martin Buchkovich, Q2 Solutions Genomics  


  • OMAS-associated neuroblastomas contain more B and T cells than control neuroblastomas
  • OMAS-associated neuroblastoma B and T cell repertoires are diverse, with small clones
  • Tertiary lymphoid structures are enriched in OMAS-associated neuroblastomas
  • Gene expression correlated to neurological symptom severity nominates autoantigens


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.


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