Disulfiram Plus Nivolumab in Patients with Advanced Gastric Cancer: An Open-Label Phase I Trial. Disulfiram Plus Nivolumab in Patients with Advanced Gastric Cancer: An Open-Label Phase I Trial

Tumor-associated macrophages correlate with poor prognosis and resistance to immune checkpoint inhibitor therapy in cancer patients. Disulfiram, a drug for alcoholism treatment, has been identified as an inhibitor for FROUNT, which facilitates chemokine-mediated macrophage accumulation to tumor sites. A combination of disulfiram with a PD-1 antibody synergistically inhibits tumor progression in the mouse model. Here, we performed the single-cell transcriptome analysis of gastric cancer specimens before and after treatment with disulfiram plus nivolumab. We explored the immunophenotypical features associated with the response to the treatment. Overall design: Thirteen patients with gastric cancer were treated with orally administered disulfiram of 160mg 3 times daily for 28 days with intravenous nivolumab 240 mg/body every two weeks with one cycle as four weeks until disease progression or up to six cycles. Specimens were collected once before and after the end of the treatment.

肿瘤相关巨噬细胞（Tumor-associated macrophages, TAMs）与癌症患者的不良预后及免疫检查点抑制剂治疗耐药性显著相关。用于戒酒治疗的双硫仑已被鉴定为FROUNT的抑制剂，而FROUNT可介导趋化因子驱动的巨噬细胞向肿瘤部位募集。双硫仑联合PD-1抗体可在小鼠模型中协同抑制肿瘤进展。本研究对双硫仑联合纳武利尤单抗治疗前后的胃癌标本开展了单细胞转录组分析，以探索与治疗响应相关的免疫表型特征。实验设计概述：13例胃癌患者接受如下治疗方案：口服双硫仑160mg/次，每日3次，持续28天；同时静脉输注纳武利尤单抗240mg/体，每2周一次，每治疗周期为4周，直至疾病进展或最多完成6个周期。分别于治疗前及治疗结束后各采集一次标本。