颅内神经母细胞瘤是发育中的外周神经系统致命的儿童实体瘤。2%的患有神经母细胞瘤的儿童会发展出醒目性肌阵挛共济失调综合症（Opsoclonus Myoclonus Ataxia Syndrome, OMAS），这是一种由小脑和脑干自身免疫引起的副肿瘤性疾病，但一般肿瘤相关结果是杰出的。我们比较了来自38例患有神经母细胞瘤的OMAS患者和26例非OMAS相关的神经母细胞瘤的肿瘤转录组和肿瘤浸润的T和B细胞的重组序列。我们发现OMAS相关肿瘤中有更多的B和T细胞浸润，同时表明它们都是多克隆扩增的。OMAS相关肿瘤中富集了三级淋巴结构（TLS）。我们发现OMAS患者中主要组织相容性复合物（MHC）II类等位基因HLA-DOB*01:01明显富集。OMAS严重程度评分与一些候选自身免疫基因的表达相关。我们提出了一个模型，其中多克隆自反应B淋巴细胞作为抗原递呈细胞，推动TLS的形成，从而支持持续多克隆T细胞介导的抗肿瘤免疫和副肿瘤性OMAS神经病理学。版权所有©2023 作者。Elsevier Inc.保留所有权利。

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.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.