Analysis of the T-Cell Receptor Repertoires of Tumor-Infiltrating Conventional and Regulatory T Cells Reveals No Evidence for Conversion in Carcinogen-Induced Tumors

A significant enrichment of CD4+Foxp3+ T cells (Tregs) is frequently observed in murine and human carcinomas. As Tregs can limit effective anti-tumor immune responses, thereby promoting tumor progression, it is important that the mechanisms underpinning intra-tumoral accumulation of Tregs are identified. Due to evidence gathered mostly in vitro, the conversion of conventional T cells (Tconv) into Tregs has been proposed as one such mechanism. We assessed the contribution of conversion in vivo by analyzing the TCR repertoires of Tconv and Treg cells in carcinogen-induced tumors in mice. Our results indicate that the TCR repertoires of Treg and Tconv cells within tumor-infiltrating lymphocytes (TILs) are largely distinct. Indeed, the cell population with the greatest degree of repertoire similarity with tumor-infiltrating Tregs was the Treg population from the tumor draining lymph node. These findings demonstrate that conversion of Tconv cells does not contribute significantly to the accumulation of tumor-infiltrating Tregs; rather, Tconv and Treg cells arise from different populations with unique TCR repertoires. Enrichment of Tregs within TILs most likely, therefore, reflects differences in the way that Treg and Tconv cells are influenced by the tumor microenvironment. Elucidating the nature of these influences may indicate how the balance between tumor-infiltrating Treg and Tconv cells can be manipulated for therapeutic purposes.