T-HELPER 1 CYTOKINE MESSENGER-RNA IS INCREASED IN SPONTANEOUSLY REGRESSING PRIMARY MELANOMAS

Spontaneous tumor regression, which is observed clinically and histolo gically in some primary melanomas, occurs in the absence of any effect ive therapy, It is probably immunologically mediated, because regressi ng melanomas are infiltrated with larger numbers of activated T cells, primarily CD4+, than non-regressing melanomas, To investigate the hyp othesis that spontaneous regression of melanomas is caused by T-cell c ytokine production, cytokine mRNA expression in 20 primary melanomas w as 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. mRN A for CD3 delta, lymphotoxin (TNF-beta), and IL-2 were significantly e levated in the ten regressing melanomas compared to the ten non-regres sing melanomas, IFN-gamma mRNA was also elevated in regressing melanom as but failed to reach statistical significance. The Th2 cytokines IL- 10 and IL-13 did not show differences in the regressing melanomas comp ared to nonregressing melanomas; neither did the pro-inflammatory cyto kines IL-1 alpha, IL-1 beta IL-6, IL-8, and TNF-alpha, nor the growth factors, bFGF and TGF-beta 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 findin gs support our hypothesis that activated CD4+ T cells may mediate mela noma regression by secretion of Th1 cytokines.