Abstract
In this study, we have identified, for the first time, the presence of de novo cellular immune reactivity against the transcription factor SOX10, using tumor-infiltrating lymphocytes obtained from a patient who experienced a dramatic clinical response to immunotherapy. SOX10 acts as a critical transactivator of tyrosinase-related protein-2 during melanoblast development and a potent transactivator of micropthalmia-associated transcription factor, which is considered to be a master gene that controls the development and postnatal survival of melanocytes. Mutations in SOX10 result in Waardenburg syndrome type 4. The overlapping epitopes AWISKPPGV and SAWISKPPGV, designated SOX10: 332-340 and SOX10: 331-340, respectively, were recognized by tumor-infiltrating lymphocyte clone M37 in an HLA-A2-restricted fashion.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antigens, Neoplasm / biosynthesis
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology*
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Clone Cells
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DNA, Complementary / genetics
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / immunology*
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Epitopes, T-Lymphocyte / immunology
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Female
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High Mobility Group Proteins / biosynthesis
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High Mobility Group Proteins / genetics
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High Mobility Group Proteins / immunology*
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Humans
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Immunotherapy, Active
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Lymphocytes, Tumor-Infiltrating / immunology
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Melanoma / genetics
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Melanoma / immunology*
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Melanoma / therapy
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Middle Aged
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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SOXE Transcription Factors
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Transcription Factors
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Waardenburg Syndrome / genetics
Substances
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Antigens, Neoplasm
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DNA, Complementary
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DNA-Binding Proteins
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Epitopes, T-Lymphocyte
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High Mobility Group Proteins
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RNA, Messenger
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SOX10 protein, human
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SOXE Transcription Factors
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Transcription Factors