T Helper 1 Cytokine mRNA Is Increased in Spontaneously Regressing Primary Melanomas

Abstract

Spontaneous tumor regression, which is observed clinically and histologically in some primary melanomas, occurs in the absence of any effective therapy. It is probably immunologcally mediated, because regressing melanomas are infiltrated with larger number of activated T cells, primarily CD4+, than non-regressing melanomas. To investigate the hypothesis that spontaneous regression of melanomas is caused by T-cell cytokine production, cytokine mRNA expression in 20 primary melanomas was examined using a noncompetitive, quantitative reverse-transcriptase polymerase chain reaction method. DNA standards were used to generate known numbers of molecules in each sample. Results were standardized to the internal control, glyceraldehyde-3-phosphate dehydrogenase. mRNA for CD3δ, lymphotoxin (TNF-β), and IL-2 were significantly elevated in the ten regressing melanomas compared to the ten non-regressing melanomas. IFN-γ mRNA was also elevated in regressing melanomas but failed to reach statistical significance. The Th2 cytokines IL-10 and IL-13 did not show differences in the regressing melanomas compared to nonregressing melanomas; neither did the pro-inflammatory cytokines IL-1α, IL- 1β, IL-6, IL-8, and TNF-α, nor the growth factors, bFGF and TGF-β or GM-CSF. This study shows an association between Th1 cytokines and spontaneously regressing melanomas. Although we have not shown that these cytokines cause regression, these findings support our hypothesis that activated CD4+ T cells may mediate melanoma regression by secretion of Th1 cytokines