Tumor microenvironment is composed of tumor cells, fibroblasts, and infiltrating immune cells, and other cellular components, which work together and create an inflammatory environment favoring tumor progression. The present study aimed to characterize the expression and location of immune cells and investigate inflammatory factors that influence pancreatic ductal adenocarcinoma (PDAC).
Methods: qPCRs and immunohistological stainings were performed for inflammatory factors and immune cells localized in tumor tissues from patients with PDAC (N=30).
Results: All PDAC tissues had significant increased levels of inflammatory and chemotactic factors such as IL-1α, COX-2, CXCL8, CCL2, and CCL20 as compared to controls. The PDAC stroma, i.e. the fibrosis surrounding the tumor, was the main producer of these factors with the exception of IL-1α, which was expressed by tumor cells and some infiltrating immune cells. The gene expression for immune cell specific markers CD163, CD1c, CD303, and CD8, corresponding to macrophages, myeloid dendritic cells (DCs), plasmacytoid DCs, and cytotoxic T lymphocytes (CTL), respectively, were all significantly increased in PDAC tissues. Immunostaining of the tumor tissue confirmed the elevated levels of infiltrating macrophages, DCs, mature DCs, and cytotoxic T lymphocytes (CTL). The different immune cells were in nearly all cases localized in the fibrotic tissue adjacent to tumor nests. Production of CXCL8 mRNA and protein by the stroma was dependent on the tumor expression of IL-1α. Of importance, we found a correlation in expression of the proinflammatory factor IL-1α and the PDAC patients’ survival time.
Conclusion: PDAC cells seem to take advantage of IL-1α to create an inflammatory microenvironment with high degree of fibrosis and the ability to both recruit and activate immune cells and the level of inflammation in this environment influenced the clinical outcome for the patients. Therapies targeting the inflammation might be beneficial for the survival of patients with PDAC.
2010. Vol. 10, no 87