Predicted Markers of Overall Survival in Pancreatic Cancer Patients Receiving Dendritic Cell Vaccinations Targeting WT1
Predicted Markers of Overall Survival in Pancreatic Cancer Patients Receiving Dendritic Cell Vaccinations Targeting WT1
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DOI：
10.1159/000500359
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发表时间：
2019-01-01
期刊：
影响因子：
3.5
通讯作者：
Koido，Shigeo
中科院分区：
文献类型：
--
作者：
Ito，Zensho;Kan，Shin;Koido，Shigeo
BackgroundWe已经开发了一种基于Wilms肿瘤1（WT 1）靶向树突状细胞（DC）的癌症疫苗联合标准化疗治疗晚期胰腺导管腺癌（PDA）患者。MethodsWe评估了PDA患者的总生存期（OS）的预测标志物，PDA患者接受多种主要组织相容性复合体I/II类限制性WT 1肽脉冲DC疫苗（DC/WT 1-I/II）联合化疗治疗。在整个免疫化疗期间，检测了7例符合条件的PDA患者的粒细胞来源的可溶性因子的血浆水平。此外，还评估了全身炎症反应标志物（嗜中性粒细胞-淋巴细胞比[NLR]、单核细胞-淋巴细胞比[MLR]和粒细胞-淋巴细胞比[GLR]）。结果与4例非超应答者（OS< 1年）相比，其余3例超应答者（OS≥ 1年）在长期治疗过程中血浆基质金属蛋白酶-9水平显著降低。5次DC/WT 1-I/II疫苗接种和3个周期吉西他滨治疗后，超应答者的NLR、MLR和GLR显著低于非超应答者。此外，细胞质WT 1的表达在PDA细胞的超应答者是相对较弱的PDA细胞中的非super-respons. ConclusionsLonged低水平的粒细胞相关的全身炎症反应后的早期治疗和低细胞质WT 1的表达在PDA细胞可能是标志物预测OS在PDA患者接受WT 1靶向免疫化疗。
BackgroundWe have developed a Wilms’ tumor 1 (WT1)-targeting dendritic cell (DC)-based cancer vaccine combined with standard chemotherapy for patients with advanced pancreatic ductal adenocarcinoma (PDA).MethodsWe evaluated predictive markers of overall survival (OS) in PDA patients treated with multiple major histocompatibility complex class I/II-restricted, WT1 peptide-pulsed DC vaccinations (DC/WT1-I/II) in combination with chemotherapy. Throughout the entire period of immunochemotherapy, the plasma levels of soluble factors derived from granulocytes of 7 eligible PDA patients were examined. Moreover, systemic inflammatory response markers (neutrophil-to-lymphocyte ratio [NLR], monocyte-to-lymphocyte ratio [MLR], and granulocyte-to-lymphocyte ratio [GLR]) were assessed. In addition, cytoplasmic WT1 expression in PDA cells was examined.ResultsCompared to the 4 non-super-responders (OS< 1 year), the remaining 3 super-responders (OS≥ 1 year) showed significantly decreased low plasma matrix metalloproteinase-9 levels throughout long-term therapy. The NLR, MLR, and GLR after 5 DC/WT1-I/II vaccinations and 3 cycles of gemcitabine were significantly lower in the super-responders than in the non-super-responders. Furthermore, the cytoplasmic WT1 expression in the PDA cells of super-responders was relatively weak compared to that in the PDA cells of non-super-responders.ConclusionsProlonged low levels of a granulocyte-related systemic inflammatory response after the early period of therapy and low cytoplasmic WT1 expression in PDA cells may be markers predictive of OS in PDA patients receiving WT1-targeting immunochemotherapy.