皮肤神经纤维瘤 (cNF) 是神经纤维瘤病 1 (NF1) 的特征，但其免疫微环境尚不完全清楚。对来自 10 名 NF1 患者的总共 61 个 cNF 进行了不同类型 T 细胞和巨噬细胞的免疫标记，细胞密度与临床特征相关。对 8 个 cNF 及其覆盖的皮肤进行了 T 细胞受体 (TCR) CDR 结构域序列分析，并对 15 个 cNF 及其覆盖的皮肤进行了质谱分析，以研究免疫相关过程。在所有 cNF 中均检测到瘤内 T 细胞。来自比研究参与者中位年龄（33 岁）更年轻的个体的肿瘤、正在生长的肿瘤以及小于数据集中位值的肿瘤显示出 T 细胞密度增加。大多数样本显示肿瘤内或肿瘤周围有 CD3 阳性细胞聚集。 TCR 测序显示，皮肤和 cNF 承载着不同的 T 细胞群，但没有检测到显性的 cNF 特异性 T 细胞克隆。 cNF 中独特的 T 细胞克隆比皮肤中的少，质谱分析表明 cNF 中与 T 细胞介导的免疫相关的蛋白质表达低于皮肤中的表达。 cNF 中存在丰富的 CD163 阳性细胞（提示 M2 巨噬细胞）。人类 cNF 具有大量可能具有肿瘤特异性的 T 细胞和巨噬细胞群。版权所有 © 2023。由 Elsevier Inc. 出版。

Cutaneous neurofibromas (cNFs) are characteristic of neurofibromatosis 1 (NF1), yet their immune microenvironment is incompletely known. A total of 61 cNFs from ten patients with NF1 were immunolabeled for different types of T cells and macrophages, and the cell densities were correlated with clinical characteristics. Eight cNFs and their overlying skin were analyzed for T cell receptor (TCR) CDR domain sequences, and mass spectrometry of 15 cNFs and the overlying skin was performed to study immune-related processes. Intratumoral T cells were detected in all cNFs. Tumors from individuals younger than the median age of the study participants (33 years), growing tumors, and tumors smaller than the dataset median showed increased T cell density. Most samples displayed intratumoral or peritumoral aggregations of CD3 positive cells. TCR sequencing showed that the skin and cNFs host distinct T cell populations while no dominant cNF-specific T cell clones were detected. Unique T cell clones were fewer in cNFs than in skin, and mass spectrometry suggested lower expression of proteins related to T cell-mediated immunity in cNFs than in skin. CD163 positive cells suggestive of M2 macrophages were abundant in cNFs. Human cNFs have substantial T cell and macrophage populations that may be tumor specific.Copyright © 2023. Published by Elsevier Inc.