Aire-Dependent Thymic Development of Tumor-Associated Regulatory T Cells.

Despite considerable interest in the modulation of tumor-associated Foxp3+ regulatory T cells (Tregs) for therapeutic benefit, little is known about the developmental origins of these cells and the nature of the antigens that they recognize. We identified an endogenous population of antigen-specific Tregs (termed MJ23 Tregs) found recurrently enriched in the tumors of mice with oncogene-driven prostate cancer. MJ23 Tregs were not reactive to a tumor-specific antigen but instead recognized a prostate-associated antigen that was present in tumor-free mice. MJ23 Tregs underwent autoimmune regulator (Aire)-dependent thymic development in both mate and female mice. Thus, Aire-mediated expression of peripheral tissue antigens drives the thymic development of a subset of organ-specific Tregs, which are likely coopted by tumors developing within the associated organ. [ABSTRACT FROM AUTHOR]