PURPOSE Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths with high recurrence after surgery due to a paucity of effective post-surgical adjuvant treatments. DC vaccines can activate multiple anti-tumor immune responses but have not been explored for post-surgery PDAC recurrence. Intraperitoneal (IP) delivery may allow increased DC vaccine dosage and migration to lymph nodes. Here, we investigated the role of prophylactic DC vaccination controlling PDAC tumor growth with IP delivery as an administration route for DC vaccination. METHODS DC vaccines were generated using ex vivo differentiation and maturation of bone marrow-derived precursors. Twenty mice were divided into four groups (n = 5) and treated with DC vaccines, unpulsed mature DCs, Panc02 lysates or no treatment. After tumor induction, mice underwent three magnetic resonance imaging scans to track tumor growth. Apparent diffusion coefficient (ADC), a quantitative magnetic resonance imaging measurement of tumor microstructure, was calculated. Survival was tracked. Tumor tissue was collected after death and stained with hematoxylin and eosin, Masson's trichrome, terminal deoxynucleotidyl transferase dUTP nick end labeling and anti-CD8 stains for histology. RESULTS DC-vaccinated mice demonstrated stronger anti-tumor cytotoxicity compared with control groups on lactate dehydrogenase assay. DC vaccine mice also demonstrated decreased tumor volume, prolonged survival and increased ΔADC compared with control groups. On histology, the DC vaccine group had increased apoptosis, increased CD8+ T cells and decreased collagen. ΔADC negatively correlated with % collagen in tumor tissues. DISCUSSION Prophylactic DC vaccination may inhibit PDAC tumor growth during recurrence and prolong survival. ΔADC may be a potential imaging biomarker that correlates with tumor histological features.

中文翻译：

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预防性树突状细胞疫苗接种可控制小鼠模型中的胰腺癌生长


目的胰腺导管腺癌（PDAC）是癌症相关死亡的第四大原因，由于缺乏有效的术后辅助治疗，其术后复发率很高。 DC 疫苗可以激活多种抗肿瘤免疫反应，但尚未针对术后 PDAC 复发进行探索。腹膜内 (IP) 递送可能会增加 DC 疫苗剂量并迁移至淋巴结。在这里，我们研究了预防性 DC 疫苗接种通过腹腔注射作为 DC 疫苗接种的给药途径来控制 PDAC 肿瘤生长的作用。方法 DC 疫苗是利用骨髓来源的前体细胞的离体分化和成熟来产生的。将 20 只小鼠分为四组 (n = 5)，并用 DC 疫苗、未脉冲的成熟 DC、Panc02 裂解物进行治疗或不进行治疗。肿瘤诱导后，小鼠接受了三次磁共振成像扫描以追踪肿瘤生长。计算表观扩散系数（ADC），这是肿瘤微观结构的定量磁共振成像测量。追踪存活情况。死亡后收集肿瘤组织并用苏木精和伊红、Masson三色、末端脱氧核苷酸转移酶dUTP缺口末端标记和抗CD8染色进行组织学染色。结果在乳酸脱氢酶测定中，与对照组相比，DC疫苗接种的小鼠表现出更强的抗肿瘤细胞毒性。与对照组相比，DC 疫苗小鼠还表现出肿瘤体积减小、存活时间延长和 ΔADC 增加。在组织学上，DC疫苗组细胞凋亡增加，CD8+T细胞增加，胶原蛋白减少。 ΔADC 与肿瘤组织中的胶原蛋白百分比呈负相关。 讨论 预防性 DC 疫苗接种可能会抑制复发期间 PDAC 肿瘤的生长并延长生存期。 ΔADC可能是与肿瘤组织学特征相关的潜在成像生物标志物。