the immune response to melanoma is limited by thymic selection of self-antigens黑色素瘤的免疫反应是由胸腺自体抗原的选择有限.pdfVIP

The Immune Response to Melanoma Is Limited by Thymic Selection of Self-Antigens ¨ 1,2 3 1,2 1,2 1,2 Ulrike Trager , Sophie Sierro , Gordana Djordjevic , Basma Bouzo , Shivani Khandwala , Antonella Meloni4, Monika Mortensen1,2,5, Anna Katharina Simon1,2* 1 MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom, 2 NIHR Biomedical Centre, Oxford, United Kingdom, 3 Ludwig Institute for Cancer Research, Epalinges, Switzerland, 4 Pediatric Clinic II, Ospedale Microcitemico and Department of Biomedical and Biotechnological Science, University of Cagliari, Cagliari, Italy, 5 Apoptosis Department and Center for Genotoxic Stress Research, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark Abstract The expression of melanoma-associated antigens (MAA) being limited to normal melanocytes and melanomas, MAAs are ideal targets for immunotherapy and melanoma vaccines. As MAAs are derived from self, immune responses to these may be limited by thymic tolerance. The extent to which self-tolerance prevents efficient immune responses to MAAs remains unknown. The autoimmune regulator (AIRE) controls the expression of tissue-specific self-antigens in thymic epithelial cells (TECs). The level of antigens expressed in the TECs determines the fate of auto-reactive thymocytes. Deficiency in AIRE leads in both humans (APECED patients) and mice to enlarged autoreactive immune repertoires. Here we show increased IgG levels to melanoma cells in APECED patients correlating with autoimmune skin fea