C-Reactive Protein Downregulates TRAIL, a Cytokine with Key Role in Cancer Immune Surveillance 

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C-reactive protein is a biomarker of acute and chronic inflammation that is frequently elevated in patients with cancer. In a study reported in Clinical Cancer Research, Secchiero and colleagues found that increased levels of C-reactive protein were associated with downregulation of TRAIL, a cytokine that plays a key role in immune surveillance against tumors.

The investigators showed that exposure in vitro to increasing C-reactive protein concentrations resulted in downregulation of TRAIL expression, at both the mRNA and protein level, in primary peripheral blood mononuclear cells and CD14-positive monocytes. TRAIL downregulation was not due to a specific toxicity or to contaminating lipopolysaccharide. C-reactive protein also downregulated TRAIL expression and release in CD14-positive monocytes after exposure to interferon-α, a potent inducer of TRAIL.

TRAIL downregulation by C-reactive protein was accompanied by a significant increase in early response growth protein-1 (Egr-1) level. Egr-1 overexpression consistently reduced TRAIL mRNA and knockdown of Egr-1 offset the ability of C-reactive protein to downregulate TRAIL, indicating that the effect of CRP on TRAIL occurs via an Egr-1-dependent pathway.

The investigators concluded, “Our findings suggest that a chronic elevation of [C-reactive protein], which occurs during systemic inflammation and often in patients with cancer, might contribute to promote cancer development and/or progression by downregulating TRAIL in immune cells.” ■

Secchiero P, et al: Clin Cancer Res 19:1949-1959, 2013