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.
Bibliographical noteFunding Information:
This work was funded by grants to M.I.R. and J.A.P. from the Pablove Foundation , the Rally Foundation , Open Hands/Overflowing Hearts Foundation , and The Truth 365 Foundation . This work was also funded by NIH grant R35 CA220500 (J.M.M.), the Giulio D’Angio Endowed Chair (J.M.M.) and RC1MD004418 to the NCI-TARGET consortium ( COG SDC grant U10 CA180899 ), NCTN Operations Center grant U10CA180886 and NCTN Statistics & Data Center grant U10CA180899 , and support from St. Baldrick's Foundation to Children’s Oncology Group .
© 2023 The Authors
- CP: Cancer
- CP: Immunology
- immune profiling