The relationships between serum cytokine levels and tumor infiltrating immune cells and their clinical significance in colorectal cancer

Abstract

Increased inflammatory cell infiltration correlates to improved survival in colorectal cancer (CRC). Development and progression of CRC is associated with alterations in serum cytokine levels but their significance is not well defined. In this study, we investigated the relationships between the serum levels of 13 cytokines and the densities of eight types of tumor infiltrating inflammatory cells and their impact on disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) in a prospectively recruited group of 147 CRC patients. There were strong positive correlations between the serum concentrations of different cytokines, as well as between the different types of tumor infiltrating immune cells, whereas the associations between serum cytokines and tumor infiltrating immune cells were generally weak. High serum IL-12 levels associated with increased densities of peritumoral CD8 1 T cells, intraepithelial CD3 1 T cells and intratumoral neutrophils, while high serum CCL4 levels associated with increased densities of peritumoral CD68 1 cells. In multivariate survival models, increased infiltration of intraepithelial CD3 1 T cells and increased serum CCL4 associated with improved DFS, whereas higher intratumoral CD83 1 dendritic cell density and increased serum interferon gamma levels associated with improved CSS and OS. Also high density of peritumoral CD3 1 T cells associated with improved CSS. In conclusion, serum cytokines and tumor infiltrating immune cells in CRC represent entities with high intragroup correlations but relatively weak intergroup correlations. The results suggest that tumor infiltrating CD3 1 T cells, CD83 1 dendritic cells, serum CCL4 and serum interferon gamma represent relevant markers of disease outcome.

Decreased serum apolipoprotein A1 levels are associated with poor survival and systemic inflammatory response in colorectal cancer

“…The presence of a systemic inflammatory response (SIR) has been linked with advanced disease and poor survival in CRC 27–30 . SIR, induced by malignancies or other conditions such as infection, inflammation or trauma, is known to result in changes in lipid metabolism 31 .…”

Role of microRNA-141 in colorectal cancer with lymph node metastasis

“…Conversely, the status of the body's immune system is also important for tumor proliferation and metastasis. The anti-tumor response is predominantly achieved by cellular immunity, and natural killer (NK) cells and T-lymphocyte subsets have been found to be implicated in tumor immune surveillance (6).…”

Decreased preoperative serum 25-Hydroxyvitamin D levels in colorectal cancer are associated with systemic inflammation and serrated morphology

“…It was recently proposed that prediagnostic vitamin D deficiency is a risk factor for CRC with intense intratumoral periglandular immune reaction23. Our analyses indicate that serum 25(OH)D concentrations positively correlate with the densities of CD1a + dendritic cells and neutrophils at the tumor stroma but not with T cells that are considered more important in tumor immunosurveillance and have better-established prognostic value2122. The mechanism and the significance of the association we observed is not clear, but may be related to the well accepted immunoregulatory role of 25(OH)D on dendritic cells24 and requires further investigation.…”

“…Immune cell infiltration has frequently been associated with improved survival in CRC2122. It was recently proposed that prediagnostic vitamin D deficiency is a risk factor for CRC with intense intratumoral periglandular immune reaction23.…”