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

Despite considerable interest in the modulation of tumor-associated Foxp3+ regulatory T cells (T-regs) 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 T-regs (termed MJ23 T-regs) found recurrently enriched in the tumors of mice with oncogene-driven prostate cancer. MJ23 T-regs were not reactive to a tumor-specific antigen but instead recognized a prostate-associated antigen that was present in tumor-free mice. MJ23 T-regs underwent autoimmune regulator (Aire)-dependent thymic development in both male and female mice. Thus, Aire-mediated expression of peripheral tissue antigens drives the thymic development of a subset of organ-specific T-regs, which are likely coopted by tumors developing within the associated organ.