Alterations of the immune system in thymic malignancies.

Normal thymic architecture is essential for the proper development of T-lymphocytes. Immature T-cell progenitors enter the thymus where through interactions with cortical and medullary thymic epithelial cells (TECs) they undergo positive and negative selection and become competent cells that do not react with self-antigens. This process requires normal thymic architecture, expression of major histocompatibility complex (MHC) class II, and normal expression of the autoimmune regulator (AIRE) gene. Thymomas are rare neoplasms of the TECs that often generate lymphocytes that mature into CD4+ and CD8+ T-lymphocytes. However, several abnormalities have been described in thymomas that may affect normal T-cell development: the tumor architecture is distorted, neoplastics expresses less MHC class II, most thymomas do not express AIRE, and production of T-regulator cells is decreased. Thymomas are associated with a variety of autoimmune disorders often linked to T-cell-mediated autoimmunity. Myasthenia gravis, the most common autoimmune disorder associated with thymoma patients, is present in 30% of patients with thymoma. Several theories attempt to explain the association of immune disorders with thymomas. These different theories are based on failure of positive and negative selection of T-lymphocytes and on autoimmunizing mechanisms in an AIRE-poor environment in the thymus. The finding that immunosurveillance against cancer may be impaired before the diagnosis of thymoma may challenge current theories and suggest a more complex defect in T-lymphocyte maturation. It is likely that a combination of mechanisms is responsible for immune disorders in patients with thymoma. More investigation is needed to clarify the basic mechanisms responsible for immune disorders in patients with thymoma.