Magnetic resonance imaging monitoring therapeutic response to dendritic cell vaccine in murine orthotopic pancreatic cancer models

[摘要] Pancreatic ductal adenocarcinoma (PDAC) carries the worst prognosis and caused one of the highest cancer-related mortalities. Dendritic cell (DC) vaccination is a promising cancer immunotherapy; however, the clinical outcomes are often poor. The administration route of DC vaccine can significantly alter the anti-tumor immune response. Here we report on the cytotoxic T lymphocyte (CTL) responses induced by DC vaccination administered via intraperitoneal (IP) for murine PDAC, and the longitudinal assessment of tumor growth and therapeutic responses using magnetic resonance imaging (MRI). In this study, we established murine orthotopic Panc02 models of PDAC and delivered apoptotic Panc02 cell-pulsed DCs via IP injection. The migration of Panc02-pulsed DCs into spleens significantly increased from 6 h to 12 h after initiation of treatment (P = 0.002), and Panc02-pulsed DCs injected via IP induced a significantly higher level of CTL responses against Panc02 cells compared to unpulsed DCs. Tumor size and tumor apparent diffusion coefficient (ADC) were measured on MR images. Tumor sizes were significantly smaller in the treated mice than in the untreated mice (P < 0.05). The reduction of tumor ADC was less in the treated mice than in the untreated mice (P < 0.05), and the changes in tumor ADC showed significant negative correlation with the changes in tumor volume (r = -0.882, 95% confidence interval, -0.967 to -0.701, P < 0.0001). These results demonstrated the efficacy of DC vaccination administered via IP injection in murine PDAC, and the feasibility of ADC measurement as an imaging biomarker for assessment of therapeutic responses in immunotherapy.

[学科分类] 肿瘤学

[关键词] Pancreatic ductal carcinoma;dendritic cell;vaccination;intraperitoneal injection;magnetic resonance imaging