Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA; Medical Student Training Program, Northwestern University, Chicago, Illinois, USA.
Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Cytotherapy. 2020 Jan;22(1):6-15. doi: 10.1016/j.jcyt.2019.12.001.
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.
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.
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.
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.
胰腺癌（PDAC）是癌症相关死亡的第四大主要原因，由于缺乏有效的术后辅助治疗，手术后复发率很高。树突状细胞（DC）疫苗可以激活多种抗肿瘤免疫反应，但尚未探索用于术后 PDAC 复发的治疗方法。腹腔（IP）给药可能允许增加 DC 疫苗剂量并迁移到淋巴结。在这里，我们研究了预防性 DC 疫苗接种控制 PDAC 肿瘤生长的作用，将 IP 给药作为 DC 疫苗接种的给药途径。
使用体外分化和成熟的骨髓来源前体来生成 DC 疫苗。将 20 只小鼠分为四组（n=5），并分别用 DC 疫苗、未脉冲成熟的 DC、Panc02 裂解物或不治疗进行处理。在诱导肿瘤后，小鼠接受了三次磁共振成像扫描以跟踪肿瘤生长。计算表观扩散系数（ADC），这是一种肿瘤微结构的定量磁共振成像测量。跟踪生存情况。死后收集肿瘤组织，并用苏木精和伊红、马松三色染色、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。
与对照组相比，乳酸脱氢酶测定法显示 DC 疫苗接种小鼠具有更强的抗肿瘤细胞毒性。与对照组相比，DC 疫苗接种组的肿瘤体积减小，存活时间延长，ΔADC 增加。在组织学上，DC 疫苗组的细胞凋亡增加，CD8+T 细胞增加，胶原减少。ΔADC 与肿瘤组织中胶原的百分比呈负相关。
预防性 DC 疫苗接种可能会抑制复发期间的 PDAC 肿瘤生长并延长生存时间。ΔADC 可能是一种潜在的影像学生物标志物，与肿瘤组织学特征相关。
