For some human cancers, elevated densities of Foxp3+ regulatory T cells (Tregs) in the tumor tissue correlate with poor prognosis, suggesting that Tregs may play a functional role in cancer progression. Despite considerable interest in the modulation of tumor-associated Tregs for therapeutic benefit, little is known about the developmental origins of these cells and the nature of the antigens that they recognize. By a TCR sequencing approach of T cells isolated from tumors of mice with oncogene-driven prostate cancer (TRAMP), we identified an endogenous population of antigen-specific Tregs found recurrently enriched in the tumors. These Tregs were not reactive to a tumor-specific antigen, but instead recognized a prostate-associated antigen that is present in tumor-free mice. Transgenic T cells expressing this Treg-derived TCR underwent Treg development in the thymus, but inefficient development in the periphery, indicating a thymic origin of these cells. Taken together, our data support a model in which organ-specific Tregs reactive to peripheral tissue antigens develop as Tregs in the thymus and are co-opted by tumors arising within the associated organ.
- Copyright © 2013 by The American Association of Immunologists, Inc.