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Published on: November 19, 2019
Prophylactic dendritic cell vaccination controls pancreatic cancer growth in a mouse model
Anna Shangguan1, Na Shang2, Matteo Figini2
1Department of Radiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA; Medical Student Training Program, Northwestern University, Chicago, Illinois, USA.
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.
Insights
Prophylactic dendritic cell (DC) vaccination may prevent pancreatic ductal adenocarcinoma (PDAC) recurrence. This study shows DC vaccines reduced tumor growth and prolonged survival in mice, with imaging biomarkers correlating to tumor histology.
Area of Science:
- Oncology
- Immunology
- Medical Imaging
Background:
- Pancreatic ductal adenocarcinoma (PDAC) has a high recurrence rate post-surgery due to limited adjuvant treatments.
- Dendritic cell (DC) vaccines show potential for activating anti-tumor immunity but haven't been studied for PDAC recurrence.
- Intraperitoneal (IP) delivery of DC vaccines may enhance dosage and lymph node migration.
Purpose of the Study:
- To investigate the efficacy of prophylactic DC vaccination in controlling PDAC tumor growth.
- To evaluate IP delivery as an administration route for DC vaccination in PDAC.
- To explore the correlation between imaging biomarkers and tumor histology.
Main Methods:
- DC vaccines were generated ex vivo from bone marrow precursors.
- Mice received DC vaccines, unpulsed DCs, tumor lysates, or no treatment after tumor induction.
- Tumor growth was monitored using MRI, calculating apparent diffusion coefficient (ADC). Survival and histological features (apoptosis, CD8+ T cells, collagen) were analyzed.
Main Results:
- DC-vaccinated mice exhibited enhanced anti-tumor cytotoxicity and prolonged survival.
- Tumor volume decreased, and survival was prolonged in the DC vaccine group.
- Increased apoptosis and CD8+ T cells, with decreased collagen, were observed in DC-vaccinated tumors. Increased ΔADC correlated with decreased collagen.
Conclusions:
- Prophylactic DC vaccination can potentially inhibit PDAC recurrence and extend survival.
- ΔADC may serve as a non-invasive imaging biomarker for assessing PDAC tumor response to DC vaccination.
