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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
O'Hara
R J
RJ
University of Hull, Academic Surgical Unit, Castle Hill Hospital, East Yorkshire, United Kingdom.
Greenman
J
J
Drew
P J
PJ
McDonald
A W
AW
Duthie
G S
GS
Lee
P W
PW
Monson
J R
JR
D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000097:blood; D008875:Middle Aged; D009367:Neoplasm Staging; D018709:Statistics, Nonparametric
D018664:Interleukin-12