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Dendritic Cell Infiltration in Colon Cancer
Thomas Schwaab1, Julia E. Weiss, Alan R. Schned
1Departments of Surgery, Community and Family Medicine, and Pathology, Dartmouth Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, New Hampshire, U.S.A.
Journal of Immunotherapy : Official Journal of the Society for Biological Therapy
|July 13, 2001
Summary
Dendritic cell (DC) density is significantly lower in colorectal cancer primaries and metastases compared to normal tissue. Tumor vascular endothelial growth factor and tumor necrosis factor expression correlate with increased mature DC infiltration.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Dendritic cells (DCs) play a crucial role in initiating anti-tumor immune responses.
- Understanding DC infiltration in colorectal cancer (CRC) is vital for developing effective immunotherapies.
Purpose of the Study:
- To quantitatively assess mature dendritic cell infiltration in primary and metastatic colorectal tumors.
- To investigate the relationship between DC density and the expression of specific cytokines and growth factors within the tumor microenvironment.
Main Methods:
- Immunohistochemistry was used to evaluate CD83, HLA-DR, CD40, and CD86 expression in colorectal cancer tissues.
- DC density was quantified and compared between primary tumors, metastatic tumors, and normal colonic mucosa.
- Correlation analysis was performed between DC density and the expression of cytokines (IL-10, TGF-β, TNF) and VEGF by tumor cells and tumor-infiltrating lymphocytes (TILs).
Main Results:
- Mature DCs (CD83+, HLA-DR+, CD40+, CD86+) were significantly less abundant in primary CRC (0.29 cells/hpf) and metastases (0.05 cells/hpf) compared to normal mucosa (0.84 cells/hpf).
- Metastatic tumors showed a sixfold lower DC density than primary tumors.
- Tumor expression of vascular endothelial growth factor (VEGF) was associated with a twofold increase in DC density.
- High expression of tumor necrosis factor (TNF) by TILs correlated with increased mature DC density in tumors.
Conclusions:
- Colorectal tumors exhibit significantly reduced infiltration of mature dendritic cells compared to normal tissue.
- VEGF and TNF show potential as positive regulators of DC infiltration in the CRC microenvironment.
- Further research into manipulating these factors could enhance anti-tumor immunity in colorectal cancer.