Whole Transcriptome Sequencing of Resectable Stage III/IV Melanoma Evaluated After Starting Hu14.18-IL2 Predicts Outcome. Whole Transcriptome Sequencing of Resectable Stage III/IV Melanoma Evaluated After Starting Hu14.18-IL2 Predicts Outcome

Background: We analyzed whole transcriptome sequencing in tumors from 23 patients with stage III or IV melanoma from a pilot trial of the anti-GD2 immunocytokine, hu14.18-IL2, to identify predictive immune and/or tumor biomarkers in melanoma patients at high risk for recurrence. Methods: Patients were randomized to receive the first of 3 monthly-courses of hu14.18-IL2 immunotherapy either before (Group A) or after (Group B) complete surgical resection of all known disease. Tumors were evaluated by histology and whole transcriptome sequencing. Results: We report here that tumor infiltrating lymphocyte (TIL) levels directly associate with relapse-free survival (RFS) and overall survival (OS) in resected tumors from Group A, where early responses to the immunotherapy agent could be assessed. TIL levels directly associated with a previously reported immune signature which associated with RFS and OS, particularly in Group A tumors. In Group A tumors there... (for more see dbGaP study page.)

背景：本研究针对一项抗GD2（GD2）免疫细胞因子hu14.18-IL2的先导临床试验中，23例III期或IV期黑色素瘤患者的肿瘤全转录组测序数据展开分析，旨在筛选复发高风险黑色素瘤患者的预测性免疫及/或肿瘤生物标志物。方法：所有已知病灶均接受根治性手术切除后，患者被随机分配至两组——A组于术前接受3个月度疗程中的首个疗程的hu14.18-IL2免疫治疗，B组则于术后接受该治疗。通过组织病理学检测及全转录组测序对肿瘤样本进行评估。结果：本研究显示，在A组经手术切除的肿瘤样本中，肿瘤浸润淋巴细胞（Tumor Infiltrating Lymphocyte, TIL）水平与无复发生存期（Relapse-Free Survival, RFS）及总生存期（Overall Survival, OS）直接相关，该组可有效评估免疫治疗药物的早期应答情况。TIL水平与此前报道的一项免疫特征直接相关，该特征与RFS及OS存在显著关联，尤其在A组肿瘤样本中更为突出。A组肿瘤样本中……（更多详情请参见dbGaP研究页面）