T helper 1 cytokine mRNA is increased in spontaneously regressing primary melanomas

J Invest Dermatol. 1997 Jun;108(6):914-9. doi: 10.1111/1523-1747.ep12292705.

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 immunologically mediated, because regressing melanomas are infiltrated with larger numbers of activated T cells, primarily CD4+, than nonregressing 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 CD35, lymphotoxin (TNF-beta), and IL-2 were significantly elevated in the ten regressing melanomas compared to the ten nonregressing melanomas. IFN-gamma 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-1alpha, IL-1beta, 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 findings support our hypothesis that activated CD4+ T cells may mediate melanoma regression by secretion of Th1 cytokines.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • CD3 Complex / analysis
  • CD3 Complex / genetics
  • CD3 Complex / metabolism
  • DNA Primers / analysis
  • DNA Primers / chemistry
  • DNA Primers / genetics
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / chemistry
  • DNA, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glyceraldehyde-3-Phosphate Dehydrogenases / analysis
  • Glyceraldehyde-3-Phosphate Dehydrogenases / genetics
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / analysis
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Growth Substances / analysis
  • Growth Substances / genetics
  • Growth Substances / metabolism
  • Humans
  • Interferon-gamma / analysis
  • Interferon-gamma / genetics*
  • Interferon-gamma / metabolism
  • Interleukin-2 / analysis
  • Interleukin-2 / genetics*
  • Interleukin-2 / metabolism
  • Interleukins / analysis
  • Interleukins / genetics
  • Interleukins / metabolism
  • Lymphotoxin-alpha / analysis
  • Lymphotoxin-alpha / genetics*
  • Lymphotoxin-alpha / metabolism
  • Male
  • Melanoma / chemistry*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Middle Aged
  • Neoplasm Regression, Spontaneous / genetics*
  • Neoplasm Regression, Spontaneous / pathology
  • Neoplasm Regression, Spontaneous / physiopathology
  • RNA, Messenger / analysis*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Skin / chemistry
  • Skin / metabolism
  • Skin / pathology
  • Skin Neoplasms / chemistry*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology

Substances

  • CD3 Complex
  • DNA Primers
  • DNA, Neoplasm
  • Growth Substances
  • Interleukin-2
  • Interleukins
  • Lymphotoxin-alpha
  • RNA, Messenger
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Glyceraldehyde-3-Phosphate Dehydrogenases