Local expression of cytokines in human colorectal carcinoma: evidence of specific interleukin-6 gene expression.
The expression of cytokine mRNAs in tumor tissue, normal mucosa, and peripheral blood mononuclear cells (PBMCs) was studied in 12 patients with colorectal cancer undergoing surgical resection, to characterize local immune conditions. mRNA transcripts for interleukin (IL)-1 beta, IL-2, IL-2-R(p55), IL-4, IL-5, IL-6, and IL-10 were detected using the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. IL-6 mRNA was expressed in tumor tissue in 83% of the cases but only in one case in normal mucosa (p < 0.001); serum levels of IL-6 did not show any correlation with IL-6 mRNA; IL-1 beta transcripts were present in all tumor tissue samples; no IL-4 expression was detected; IL-2 mRNA was only present in two tumors; IL-2R(p55) mRNA was found in 58% of tumors but not in normal mucosae (p = 0.005). The expression of IL-10 suggests that it does not play a central role in colorectal cancer immunosuppression, and cytokine expression in PBMCs indicates a different and independent activation. This study suggests a pattern of expression of inflammatory cytokines in the tumor microenvironment, probably produced by infiltrating immune cells. The absence of the specific immune-activating cytokines, IL-2 and IL-4, could indicate an impairment of the anticancer immune response; IL-2R results confirm the dysregulation of the IL-2/IL-2R activation pathway. These findings may lead to a better understanding of the role of cytokines and especially IL-6 at the tumor site and hence their importance in developing an effective immunotherapy.