Division of Oncology and Pathology, Department of Clinical Sciences Lund, Faculty of Medicine, Lund University, Scheelegatan 2, Medicon Village, 22185, Lund, Sweden.
Center for Cancer Immune Therapy, Department of Hematology, Herlev Ringvej 75, 2730, Herlev, Denmark.
Nat Commun. 2017 Nov 23;8(1):1738. doi: 10.1038/s41467-017-01460-0.
Adoptive T-cell therapy (ACT) is a highly intensive immunotherapy regime that has yielded remarkable response rates and many durable responses in clinical trials in melanoma; however, 50-60% of the patients have no clinical benefit. Here, we searched for predictive biomarkers to ACT in melanoma. Whole exome- and transcriptome sequencing and neoantigen prediction were applied to pre-treatment samples from 27 patients recruited to a clinical phase I/II trial of ACT in stage IV melanoma. All patients had previously progressed on other immunotherapies. We report that clinical benefit is associated with significantly higher predicted neoantigen load. High mutation and predicted neoantigen load are significantly associated with improved progression-free and overall survival. Further, clinical benefit is associated with the expression of immune activation signatures including a high MHC-I antigen processing and presentation score. These results improve our understanding of mechanisms behind clinical benefit of ACT in melanoma.
过继性 T 细胞疗法（ACT）是一种高度强化的免疫疗法方案，在黑色素瘤的临床试验中产生了显著的反应率和许多持久的反应；然而，50-60%的患者没有临床获益。在这里，我们寻找预测 ACT 在黑色素瘤中的生物标志物。对 27 名接受 IV 期黑色素瘤 ACT 临床 I/II 期试验的患者的预处理样本进行了全外显子组和转录组测序以及新抗原预测。所有患者之前都接受过其他免疫疗法的治疗。我们报告说，临床获益与预测的新抗原负荷显著增加有关。高突变和预测的新抗原负荷与无进展生存期和总生存期的改善显著相关。此外，临床获益与免疫激活特征的表达有关，包括 MHC-I 抗原加工和呈递评分高。这些结果提高了我们对 ACT 在黑色素瘤中临床获益背后机制的理解。
