胰腺癌空间构型与新辅助治疗和根治性切除术后疾病复发相关
Spatial Configuration of Pancreatic Cancer Is Associated with Disease Recurrence after Neoadjuvant Therapy and Curative-Intent Resection.
从标准H&E切片量化的残留癌-间质拓扑结构在PDAC新辅助治疗后产生独立预后信号,为空间风险提供细胞免疫相关性依据,并推动前瞻性验证及空间信息指导的辅助治疗策略。
英文原题:Baseline immunity predicts prognosis of pancreatic cancer patients treated with WT1 and/or MUC1 peptide-loaded dendritic cell vaccination and a standard chemotherapy.
这些结果表明,基于DC的免疫治疗联合常规化疗对晚期PDAC患者是安全的,并具有临床获益。
尽管近年来引入了免疫检查点抑制剂,但晚期胰腺癌患者的预后仍然很差。因此,迫切需要开发新的治疗方法。在本项I/II期研究中,我们评估了负载Wilms瘤1(WT1)和/或黏蛋白1(MUC1)肽的树突状细胞(DC)疫苗联合吉西他滨加白蛋白结合型紫杉醇化疗或由奥沙利铂、伊立替康、氟尿嘧啶和亚叶酸组成的联合化疗方案(FOLFIRINOX)在晚期或复发胰腺导管腺癌(PDAC)患者中的安全性、疗效及预后因素。共纳入48例符合条件的患者,约每2-4周接受一次疫苗接种,至少接种七次。未观察到与疫苗接种相关的严重不良事件。中位无进展生存期和总生存期分别为8.1个月和15.1个月。DC疫苗接种增强了肿瘤特异性免疫,这可能与临床结局相关。多因素分析表明,DC疫苗接种前WT1或MUC1特异性干扰素ɤ酶联免疫斑点数是与总生存期相关的独立预后因素。这些结果表明,基于DC的免疫治疗联合常规化疗是安全的,对晚期PDAC患者具有临床获益。准确评估基线抗肿瘤特异性免疫对于预测临床结局至关重要。
The prognosis of patients with advanced pancreatic cancer is poor despite the recent introduction of immune checkpoint inhibitors. Therefore, the development of new therapeutic approaches is urgently required. In the present phase I/II study, we have evaluated the safety, the efficacy and the prognostic factors of Wilms' tumor 1 (WT1) and/or mucin 1 (MUC1) peptide-loaded dendritic cell (DC) vaccination in combination with a chemotherapy employing gemcitabine plus nab-paclitaxel or a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX) in patients with advanced or relapsed pancreatic ductal adenocarcinoma (PDAC). Forty-eight eligible patients were enrolled and received the vaccinations approximately every 2-4 weeks at least seven times. No severe adverse events related to the vaccinations were observed. Median progression free survival and overall survival were 8.1 months and 15.1 months, respectively. DC vaccinations augmented tumor specific immunity which might be related to clinical outcome. The multivariate analyses demonstrated that WT1 or MUC1-specific interferonɤ enzyme-linked immunospot number prior to DC vaccination was an independent prognostic factor related to overall survival. These results indicate that DC-based immunotherapy combined with a conventional chemotherapy is safe and has clinical benefits for patients in advanced stage of PDAC. The precise evaluation of the baseline antitumor specific immunity is critical to predict clinical outcome.
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