| Autor: |
MI Rosenberg, E Greenstein, M Buchkovich, M Mikl, A Peres, E Santoni-Rugiu, D Reshef, A Salovin, DL Gibbs, MS Irwin, A Naranjo, I Ulitsky, PA de Alarcon, V Weigman, G Yaari, JA Panzer, N Friedman, JM Maris |
| Rok vydání: |
2021 |
| Popis: |
SummaryNeuroblastoma 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, but unexpectedly showed that both were polyclonal expansions. Tertiary lymphoid structures (TLS) were enriched in OMAS-associated tumors. We identified significant enrichment of the 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 autoreactive B lymphocytes act as antigen presenting cells and drive TLS formation, thereby crucially supporting both sustained polyclonal T-cell-mediated anti-tumor immunity and paraneoplastic OMAS neuropathology. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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