描绘恶性外周神经鞘瘤中 T 细胞功能障碍和排除特征，揭示其对免疫治疗的敏感性。

Characterizing T-cell dysfunction and exclusion signatures in malignant peripheral nerve sheath tumors reveals susceptibilities to immunotherapy.

机构信息

Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA.

Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

出版信息

J Neurooncol. 2023 Sep;164(3):693-699. doi: 10.1007/s11060-023-04467-4. Epub 2023 Sep 27.

DOI:10.1007/s11060-023-04467-4

PMID:37755632

Abstract

PURPOSE

Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that arise from peripheral nerves and are the leading cause of mortality in Neurofibromatosis Type 1 (NF1). In this study, we characterized whether transcriptomic signatures of T-cell dysfunction (TCD) and exclusion (TCE) that inversely correlate with response to immune checkpoint blockade (ICB) immunotherapy exist in MPNSTs.

METHODS

MPNST transcriptomes were pooled from Gene Expression Omnibus (GEO). For each sample, a tumor immune dysfunction and exclusion (TIDE) score, TCD and TCE subscores, and cytotoxic T-cell(CTL) level were calculated. In the TIDE predictive algorithm, tumors are predicted to have an ICB response if they are either immunologically hot (CTL-high) without TCD or immunologically cold (CTL-low) without TCE. TIDE scores greater than zero correspond with ICB nonresponse.

RESULTS

73 MPNST samples met inclusion criteria, including 50 NF1-associated MPNSTs (68.5%). The average TIDE score was + 0.41 (SD = 1.16) with 22 (30.1%) predicted ICB responders. 11 samples were CTL-high (15.1%) with an average TCD score of + 0.99 (SD = 0.63). Among 62 CTL-low tumors, 21 were predicted to have ICB response with an average TCE score of + 0.31(SD = 1.20). Age(p = 0.18), sex(p = 0.41), NF1 diagnosis (p = 0.17), and PRC2 loss(p = 0.29) were not associated with ICB responder status.

CONCLUSIONS

Transcriptomic analysis of TCD and TCE signatures in MPNST samples reveals that a select subset of patients with MPNSTs may benefit from ICB immunotherapy.

摘要

目的

恶性外周神经鞘瘤（MPNST）是一种来源于外周神经的恶性肿瘤，是 1 型神经纤维瘤病（NF1）患者死亡的主要原因。在本研究中，我们分析了与免疫检查点阻断（ICB）免疫治疗反应呈负相关的 T 细胞功能障碍（TCD）和排除（TCE）的转录组特征是否存在于 MPNST 中。

方法

从基因表达综合数据库（GEO）中汇集 MPNST 转录组数据。对于每个样本，计算肿瘤免疫功能障碍和排除（TIDE）评分、TCD 和 TCE 子评分以及细胞毒性 T 细胞（CTL）水平。在 TIDE 预测算法中，如果肿瘤 CTL 高（CTL-high）且无 TCD，或者 CTL 低（CTL-low）且无 TCE，则预测其对 ICB 有反应。TIDE 评分大于 0 对应于 ICB 无反应。

结果

73 例 MPNST 样本符合纳入标准，包括 50 例 NF1 相关 MPNST（68.5%）。平均 TIDE 评分为+0.41（标准差[SD] = 1.16），22 例（30.1%）预测为 ICB 反应者。11 例为 CTL-high（15.1%），平均 TCD 评分为+0.99（SD = 0.63）。在 62 例 CTL-low 肿瘤中，21 例预测为 ICB 反应者，平均 TCE 评分为+0.31（SD = 1.20）。年龄（p = 0.18）、性别（p = 0.41）、NF1 诊断（p = 0.17）和 PRC2 缺失（p = 0.29）与 ICB 反应者状态无关。