Impaired interleukin-12 production is associated with a defective anti-tumor response in colorectal cancer.

Abstract

Despite development of many chemotherapeutic regimens, colorectal cancer continues to have a high mortality. One of the major new potential therapies is interleukin-12, a heterodimeric cytokine produced by antigen presenting cells. In vitro and in vivo studies have demonstrated the role of interleukin-12 in stimulating a cell-mediated anti-tumor response against a number of colon adenocarcinoma tumor models. However, it is unknown whether patients with colorectal cancer have impaired interleukin-12 production. A study was performed to investigate production of interleukin-12 preoperatively and the relationship between these levels and disease stage at surgery. Preoperative peripheral blood mononuclear cells from colorectal cancer patients and age-matched controls were stimulated by Staphylococcus aureus Cowan's Strain 1 (0.0075 percent wt/vol) in vitro for 24 hours. Expression of interleukin-12 was then assessed by enzyme-linked immunosorbent assay. A single pathologist assessed the tumors for stage according to TNM and Dukes classifications. Twenty-eight patients with colorectal cancer and 14 controls were recruited for the study. Interleukin-12 production was significantly impaired in patients with colorectal cancer compared with controls (P = 0.014), especially those with advanced disease: Dukes C, P = 0.001 and T4, P < 0.05. Interleukin-12 production is impaired in patients with colorectal cancer, especially those with advanced disease, suggesting a defective Thl-mediated anti-tumor response. These patients may well benefit from exogenous interleukin-12 treatment.