Impact of 5-Fu/oxaliplatin on mouse dendritic cells and synergetic effect with a colon cancer vaccine
Open accessAbstract
OBJECTIVE: The aim of the present study was to investigate the effects of 5-fluorouracil (5-Fu) and oxaliplatin on the function and activation pathways of mouse dendritic cells (DCs), and to clarify whether 5-Fu/oxaliplatin combined with the CD1d-MC38/α-galactosylceramide (α-GC) tumor vaccine exhibits synergistic effects on the treatment of colon cancer in mice. METHODS: culture. DC phenotypic changes were detected by flow cytometry, and the secretion of DC cytokines was detected by cytometric bead array (CBA). A MC38 mouse colon cancer model was constructed and the DCs were isolated from the spleen, tumor tissue and lymph nodes following intraperitoneal injection of 5-Fu/oxaliplatin. The cell phenotypes were detected by flow cytometry. The tumor infiltrating leukocytes, splenocytes and lymph node cells were co-cultured with the dead MC38 tumor cells, and the secretion levels of interferon-γ (IFN-γ) were detected. 5-Fu/oxaliplatin combined with our previously developed CD1d-MC38/α-GC tumor vaccine was used to inhibit the growth of MC38 colon cancer in mice, and the tumor growth rate and survival time were recorded. RESULTS: , while it could reduce the expression of programmed death ligand 1/2 (PD-L1/L2) and promote interleukin-12 (IL-12) secretion by DCs. Furthermore 5-Fu/oxaliplatin was beneficial to the differentiation of T-helper 1 (Th1) cells. 5-Fu/oxaliplatin further enhanced the stimulating phenotypic expression of DCs in tumor bearing mice, decreased PD-L1/L2 expression, and specifically activated the lymphocytes. The CD1d-MC38/α-GC tumor vaccine combined with 5-Fu/oxaliplatin could exert a synergistic role that resulted in a significant delay of the tumor growth rate, and an increase in the survival time of tumor bearing mice. CONCLUSIONS: 5-Fu/oxaliplatin decreased the expression of the DC inhibitory phenotypes PD-L1/L2, promoted DC phenotypic maturation in tumor bearing mice, activated the lymphocytes of tumor bearing mice, and exerted synergistic effects with the CD1d-MC38/α-GC colon cancer tumor vaccine.
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Chemotherapeutic drugs such as vinblastine, 5-fluorouracil, and oxaliplatin could directly enhance the functions of DC and promote IL-12 secretion.
“Also, chemotherapeutic drugs such as vinblastine, 5-fluorouracil, and oxaliplatin, could directly enhance the functions of DC and promote IL-12 secretion [49, 50].”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [50]
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- Authors
- Hong, X., Department of General Surgery, Z. H., Dong, T., Yi, T., Hu, J., Zhang, Z., Lin, S., & Niu, W.
- Affiliations
- Fudan University (CN)
- Corresponding author
- Niu, Weixin
- Venue
- Chinese Journal of Cancer Research
- Publisher
- Chinese Journal of Cancer Research
- Published
- 2018
- Volume
- 30
- Issue
- 2
- Pages
- 197-208
- ISSN
- 1000-9604 (ISSN-L)
- PMC
- PMC5953956
- OpenAlex
- W2800046601
- Cited by
- 23
- References
- 32
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 2 · 2019: 1 · 2018: 1
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Chinese Journal of Cancer Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Cancer Research and Treatments
- Keywords
- 5-fluorouracil, oxaliplatin, dendritic cells, dendritic cell maturation, IL-12, Th1 differentiation, combination immunotherapy, tumor-infiltrating lymphocytes, interferon-gamma
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