目的:恶性周围神经鞘瘤(MPNSTs)是由周围神经引起的恶性肿瘤,是1型神经纤维瘤病(NF1)死亡的主要原因。在这项研究中,我们分析了MPNSTs中是否存在与免疫检查点阻断(ICB)免疫疗法应答呈负相关的T细胞功能障碍(TCD)和排斥(TCE)的转录组特征.
方法:从基因表达综合(GEO)合并MPNST转录组。对于每个样本,肿瘤免疫功能障碍和排斥(TIDE)评分,TCD和TCE子评分,计算细胞毒性T细胞(CTL)水平。在TIDE预测算法中,如果肿瘤是无TCD的免疫热(CTL-高)或无TCE的免疫冷(CTL-低),则预测它们具有ICB应答。TIDE评分大于零与ICB无应答相对应。
结果:73个MPNST样本符合纳入标准,包括50个NF1相关的MPNST(68.5%)。平均TIDE评分为+0.41(SD=1.16),22(30.1%)个预测ICB应答者。11个样品为CTL高(15.1%),平均TCD评分为+0.99(SD=0.63)。在62个低CTL肿瘤中,预测21具有ICB响应,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),PRC2丢失(p=0.29)与ICB应答者状态无关。
结论:MPNST样本中TCD和TCE特征的转录组学分析显示,部分MPNST患者可能受益于ICB免疫治疗。
OBJECTIVE: 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.