Fluorescence tracking Treg movement identifies anti-CCR8 and radiation as a therapeutic combination

Radiation therapy (RT) is recognized for its ability to induce DNA damage within cancer cells, leading to cancer cell death and promotion of anti-tumor immune responses. However, this beneficial effect is often counterbalanced by the presence of suppressive Tregs. Although factors such as RT-induced transforming growth factor β (TGF-β) can contribute to increased Treg accumulation within the tumor, the dynamics of Treg movement, and recruitment in the post-RT tumor microenvironment are not fully understood. Our study examined Treg migration following RT, revealing that RT disrupts Treg migration to the tumor-draining lymph node (TdLN) and alters their phenotype. Combining RT with anti-CCR8 therapy, which selectively depletes Tregs within the tumor, significantly reduced tumor burden, and increased survival in preclinical models. This combination also proved effective against distant and unirradiated tumors. Additionally, efficacy of combination therapy was CD8 T cell dependent. These findings highlight the potential of combining RT with Treg-targeting therapies to enhance anti-tumor immunity.