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 CD38, lymphotoxin (TNF-α), and IL-2 were significantly elevated in the ten regressing melanomas compared to the ten nonregressing melanomas. IFN-υ 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 IL1β, 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 914-919 |
| Number of pages | 6 |
| Journal | Journal of Investigative Dermatology |
| Volume | 108 |
| Issue number | 6 |
| State | Published - 1997 |
| Externally published | Yes |
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Keywords
- Interleukin-2
- Lymphotoxin
- Skin cancer
- Tumor regression
ASJC Scopus subject areas
- Dermatology
Cite this
T helper 1 cytokine mRNA is increased in spontaneously regressing primary melanomas. / Lowes, Michelle A.; Bishop, G. Alex; Crotty, Kerry; Barnetson, Ross St C; Halliday, Gary M.
In: Journal of Investigative Dermatology, Vol. 108, No. 6, 1997, p. 914-919.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - T helper 1 cytokine mRNA is increased in spontaneously regressing primary melanomas
AU - Lowes, Michelle A.
AU - Bishop, G. Alex
AU - Crotty, Kerry
AU - Barnetson, Ross St C
AU - Halliday, Gary M.
PY - 1997
Y1 - 1997
N2 - 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 CD38, lymphotoxin (TNF-α), and IL-2 were significantly elevated in the ten regressing melanomas compared to the ten nonregressing melanomas. IFN-υ 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 IL1β, 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.
AB - 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 CD38, lymphotoxin (TNF-α), and IL-2 were significantly elevated in the ten regressing melanomas compared to the ten nonregressing melanomas. IFN-υ 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 IL1β, 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.
KW - Interleukin-2
KW - Lymphotoxin
KW - Skin cancer
KW - Tumor regression
UR - http://www.scopus.com/inward/record.url?scp=0030948658&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030948658&partnerID=8YFLogxK
M3 - Article
C2 - 9182821
AN - SCOPUS:0030948658
VL - 108
SP - 914
EP - 919
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 6
ER -