Radiotherapy enhances innate and adaptive antitumor immunity; however, the effects of radiation on suppressive immune cells, such as regulatory T cells (Treg), in the tumor microenvironment (TME) are not fully elucidated. Although previous reports suggest an increased Treg infiltration after radiation, whether these Tregs are functionally suppressive remains undetermined.
To test the hypothesis that RT enhances the suppressive function of Treg in the TME, in the paper “Stereotactic Radiotherapy Increases Functionally Suppressive Regulatory T Cells in the Tumor Microenvironment” Muroyama Y, Nirschl TR, Kochel CM, et al, selectively irradiated implanted tumors using the Xstrahl Small Animal Radiation Research Platform (SARRP), which models stereotactic radiotherapy in human patients. These were then analyzed for tumor-infiltrating lymphocytes (TIL) with flow-cytometry and functional assays.
The data showed that radiotherapy significantly increased tumor-infiltrating Tregs (TIL-Treg), which had higher expression of CTLA-4, 4-1BB, and Helios compared with Tregs in nonirradiated tumors. This observation held true across several tumor models (B16/F10, RENCA, and MC38). It was found that TIL-Tregs from irradiated tumors had equal or improved suppressive capacity compared with nonirradiated tumors. The data also indicated that after radiotherapy, Tregs proliferated more robustly than other T-cell subsets in the TME. In addition, after radiotherapy, expansion of Tregs occurred when T-cell migration was inhibited using Fingolimod, suggesting that the increased Treg frequency was likely due to preferential proliferation of intratumoral Treg after radiation. The data also suggested that Treg expansion after irradiation was independent of TGFβ and IL33 signaling.
Therefore it was concluded that the data demonstrated radiotherapy increased phenotypically and functionally suppressive Tregs in the TME. The results suggest that radiotherapy might be combined effectively with Treg-targeting agents to maximize antitumor efficacy.
This Xstrahl In Action was adapted from a article found on a National Library of Medicine website.