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Inhibition of melanoma growth after treatment with dendritic cells in a Tyr-SV40E murine model requires CD4+ T cells but not CD8+ T cells.
- Source :
-
Melanoma research [Melanoma Res] 2004 Dec; Vol. 14 (6), pp. 555-62. - Publication Year :
- 2004
-
Abstract
- Melanomas are promising targets for immunotherapy, as they express a number of tissue-specific antigens against which immune responses can be elicited. We have previously described transgenic mice in which malignant cutaneous melanomas are produced. The 1042 melanoma cell line, derived from a primary melanoma in one of these mice, was used here to generate tumours by subcutaneous inoculation in syngeneic animals. All mice injected with 1 x 10(6) cells of the 1042 cell line developed a tumour. CD4+ T cells, CD8+ T cells and macrophages infiltrated the tumours. Treatment with dendritic cells pulsed with peptides from melanogenic proteins slowed tumour growth and resulted in increased numbers of infiltrating lymphocytes and macrophages, expansion of CD4+ T cells specific for 1042 cell antigens, and increased levels of 1042-specific immunoglobulin G1 (IgG1) and IgM in serum. The frequency of cytotoxic T lymphocytes (CTLs) specific for the MART-1 melanocytic antigen did not increase after dendritic cell treatment. Indeed, the presence of CD8+ T cells was apparently not required for the anti-tumour effects: slowing of tumour growth was not abrogated in animals depleted of CD8+ T cells using antibodies, or in syngeneic CD8-/- animals. In contrast, treatment with dendritic cells + peptides was ineffective after depletion of CD4+ T cells and in syngeneic CD4-/- mice. This experimental system therefore provides an opportunity to investigate CD4-dependent anti-tumour effector mechanisms, and for studies designed to activate the quiescent CTLs which infiltrate melanomas.
- Subjects :
- Animals
Antigens, Neoplasm
Cell Proliferation
Cells, Cultured
Cytokines metabolism
Cytotoxicity Tests, Immunologic
Dendritic Cells metabolism
Immunoglobulin G blood
Lymphocytes, Tumor-Infiltrating immunology
MART-1 Antigen
Macrophages
Melanoma, Experimental immunology
Melanoma, Experimental pathology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Monophenol Monooxygenase immunology
Monophenol Monooxygenase metabolism
Neoplasm Proteins metabolism
Peptide Fragments metabolism
Simian virus 40 immunology
Simian virus 40 metabolism
Skin Neoplasms immunology
Skin Neoplasms pathology
Skin Neoplasms therapy
T-Lymphocytes, Cytotoxic
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Dendritic Cells immunology
Melanoma, Experimental therapy
Monophenol Monooxygenase genetics
Peptide Fragments immunology
Simian virus 40 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0960-8931
- Volume :
- 14
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Melanoma research
- Publication Type :
- Academic Journal
- Accession number :
- 15577330
- Full Text :
- https://doi.org/10.1097/00008390-200412000-00019