Abstract
IFN-γ released from cytotoxic T lymphocytes (CTLs) during the effector phase is essential for rejecting bulky melanoma tumors. In contrast, IFN-γ is known to induce certain immunosuppressive factors in tumor cells such as programmed cell death 1 ligand 1 (PD-L1). In this study, we have identified candidates for IFN-γ-inducible CTL-suppressive factors in melanoma cells using complementary DNA microarray analysis, and CD271/p75/neurotrophin receptor (NTR) was one of the candidate genes. Recently, CD271 was identified as a marker of the cancer stem cell-like population in human melanoma tissues. In this study, we showed that overexpression of CD271 on melanoma cells suppressed the in vitro activation of melanoma-specific CTLs. This suppression was mediated by CD271 ligation with activated CTL-derived nerve growth factor and the subsequent downregulation of melanoma antigens. Moreover, we found that the expression levels of PD-L1 on melanoma cells correlated with those of CD271, and they additively suppressed the activation of melanoma-specific CTLs. To the best of our knowledge, the role of overexpression of CD271 in an anti-melanoma T-cell response has been unreported.
MeSH terms
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B7-H1 Antigen / metabolism
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Biomarkers, Tumor / metabolism
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Cell Line, Tumor
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Down-Regulation / drug effects
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Down-Regulation / immunology
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Humans
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Immune Tolerance / drug effects
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Immune Tolerance / physiology*
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Interferon-gamma / immunology*
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Interferon-gamma / pharmacology
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MART-1 Antigen / metabolism
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Melanoma / immunology*
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Melanoma / metabolism
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Melanoma / pathology
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Melanoma-Specific Antigens / genetics
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Melanoma-Specific Antigens / immunology
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Melanoma-Specific Antigens / metabolism
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / immunology*
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Nerve Tissue Proteins / metabolism
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Oligonucleotide Array Sequence Analysis
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Receptors, Nerve Growth Factor / genetics
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Receptors, Nerve Growth Factor / immunology*
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Receptors, Nerve Growth Factor / metabolism
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Skin Neoplasms / immunology*
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Skin Neoplasms / metabolism
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Skin Neoplasms / pathology
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism
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Up-Regulation / drug effects
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Up-Regulation / immunology
Substances
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B7-H1 Antigen
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Biomarkers, Tumor
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CD274 protein, human
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MART-1 Antigen
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MLANA protein, human
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Melanoma-Specific Antigens
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NGFR protein, human
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Nerve Tissue Proteins
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Receptors, Nerve Growth Factor
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Interferon-gamma