Background/Objectives: Peripheral neuroblastic tumors (pNT) are a biologically heterogeneous group of embryonal tumors that derive from the neural crest and affect the sympathetic nervous system. So far, little is known about the complex immune landscape in these rare childhood cancers.Methods: We focused on the immune cell infiltrate of treatment-naïve pNT from 24 patients, including high-risk neuroblastoma (HR-NBL), non-high-risk neuroblastoma (NHR-NBL), ganglioneuroblastoma (GNBL), and rare ganglioneuroma (GN). To gain novel insights into the immune architecture of these pNT subtypes, we used multiplex immunohistochemistry, multispectral imaging, and algorithm-based data evaluation to detect and characterize T cells, B cells, neutrophils, macrophages, and tertiary lymphoid structures (TLS).Results: The majority of the investigated tumor-infiltrating immune cells were macrophages and T cells. Their detailed phenotypic characterization revealed high proportions of M2-like macrophages as well as activated GrzB+CD8+and PD-1+T lymphocytes. Proportions of these T cell phenotypes were significantly increased in GN compared to HR-NBL, NHR-NBL, or GNBL. In addition, TLS occurred in 11 of 24 patients, independent of immune cell frequencies in the whole tissues. Interestingly, all GN, most GNBL, but only a few NBL contained TLS. We distinguished between three TLS maturation stages that were present irrespective of the pNT subtype. The majority belonged to mature TLS of the primary follicle state. Mature LAMP3+dendritic cells were also found, predominantly in T cell zones of TLS. Furthermore, TLS presence identified pNT patients with significantly prolonged progression-free survival in contrast to all other analyzed immunological features.Conclusions: We propose TLS to be a potential prognostic marker for pNT to predict patient outcomes.
背景/目的：外周神经母细胞瘤（pNT）是一组源自神经嵴、影响交感神经系统的胚胎性肿瘤，具有生物学异质性。目前，关于这些罕见儿童肿瘤中复杂的免疫微环境知之甚少。方法：我们聚焦于24例未经治疗pNT患者的肿瘤免疫细胞浸润情况，包括高危神经母细胞瘤（HR-NBL）、非高危神经母细胞瘤（NHR-NBL）、神经节母细胞瘤（GNBL）及罕见的神经节瘤（GN）。为深入解析这些pNT亚型的免疫结构特征，我们采用多重免疫组化、多光谱成像及算法数据分析技术，系统检测并表征了T细胞、B细胞、中性粒细胞、巨噬细胞及三级淋巴结构（TLS）。结果：肿瘤浸润免疫细胞以巨噬细胞和T细胞为主。表型分析显示M2样巨噬细胞比例较高，同时存在大量活化的GrzB+CD8+及PD-1+T淋巴细胞。与HR-NBL、NHR-NBL或GNBL相比，GN中这些T细胞表型比例显著升高。此外，24例患者中有11例出现TLS，其存在与整体组织免疫细胞频率无关。值得注意的是，所有GN、大多数GNBL及少数NBL中均检测到TLS。我们鉴定了三种TLS成熟阶段，这些阶段存在于所有pNT亚型中，其中以初级滤泡状态的成熟TLS为主。成熟LAMP3+树突状细胞主要分布于TLS的T细胞区。生存分析显示，与其他免疫学特征相比，TLS的存在与pNT患者显著延长的无进展生存期相关。结论：我们提出TLS可能作为pNT的潜在预后标志物，用于预测患者临床结局。
肿瘤(癌症)患者之家