Regulatory T Cells Play an Important Role in the Prevention of Murine Melanocytic Nevi and Melanomas.
Cancer Prev Res (Phila)
; 14(2): 165-174, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33148679
ABSTRACT
Melanocytic nevi are benign proliferations of pigment cells that can occasionally develop into melanomas. There is a significant correlation between increased nevus numbers and melanoma development. Our previous reports revealed that 7,12-dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced dysplastic nevi in C3H/HeN mice, with a potential to transform into melanomas. To understand the immune mechanisms behind this transformation, we applied increasing DMBA doses followed by TPA to the skin of C3H/HeN mice. We observed that increased doses of DMBA correlated well with increased numbers of nevi. The increased DMBA dose induced diminished immune responses and promoted the expansion of regulatory T cells (Treg) that resulted in increased IL10 and reduced IFNγ levels. Mice with increased nevus numbers had loss of p16 expression. These mice had increased migration of melanocytic cells to lymph nodes (LN) and a greater percent of LNs produced immortalized melanocytic cell lines. DMBA-induced immunosuppression was lost in CD4-knockout (KO) mice. Lymphocytes in the CD4KO mice produced less IL10 than CD8KO mice. Furthermore, CD4KO mice had significantly reduced nevus numbers and size compared with wild-type and CD8KO mice. These results suggest that Tregs play a vital role in the incidence of nevi and their progression to melanoma.Prevention Relevance There has been little progress in developing novel strategies for preventing premalignant dysplastic nevi from becoming melanomas. In this study in mice, regulatory-T cells enhanced progression of benign nevi to malignant melanomas; and by inhibiting their activity, melanomas could be retarded. The findings identify new possibilities for melanoma prevention in high risk individuals.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Cutâneas
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Melanoma Experimental
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Linfócitos T Reguladores
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Nevo Pigmentado
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article