The Waardenburg syndrome type 4 gene, SOX10, is a novel tumor-associated antigen identified in a patient with a dramatic response to immunotherapy.
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.
Khong
Hung T
HT
Affiliation Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10 Room 2B42, 10 Center Drive, Bethesda, MD 20892, USA.
Rosenberg
Steven A
SA
D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D002999:Clone Cells; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006609:High Mobility Group Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016233:Immunotherapy, Active; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D055757:SOXE Transcription Factors; D014157:Transcription Factors; D014849:Waardenburg Syndrome / Q000235:genetics
D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; D006609:High Mobility Group Proteins; D012333:RNA, Messenger; C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; D014157:Transcription Factors