Dynamic Responses of Circulating T Cells After Stereotactic Body Radiation Therapy for Bone Metastasis in Patients With Breast Cancer

Purpose: Preclinical studies have shown that radiation therapy modulates antitumor immune responses. However, circulating T-cell responses after radiation therapy in patients with cancer have been poorly characterized. This study aims to explore the changes in circulating T cells after stereotactic body radiation therapy (SBRT). Methods and Materials: Peripheral blood samples of 30 patients with breast cancer who underwent SBRT for bone metastasis were analyzed using multicolor flow cytometry. Phenotypes of PD-1⁺ CD8⁺ T cells and regulatory T (T_REG) cells were examined. Additionally, plasma protein levels were analyzed using a bead-based immunoassay. Results: Circulating PD-1⁺ CD8⁺ T cells, which are enriched for tumor-specific clonotypes, were activated at 1 week after SBRT. However, circulating T_REG cells were also activated after SBRT; this pattern was also evident among effector Foxp3^hiCD45RA⁻ T_REG cells. We observed no difference in T-cell responses according to the fraction size and number. Notably, activation of T_REG cells was more prominent in patients who experienced greater activation of PD-1⁺ CD8⁺ T cells. Plasma level changes in TGF-β1, soluble CTLA-4, and soluble 4-1BB at 1 week after SBRT were associated with PD-1⁺ CD8⁺ T-cell responses. Activation of T_REG cells at 1 week after SBRT was associated with worse progression-free survival. Clinical factors including molecular subtype were not associated with the T-cell responses. Conclusions: SBRT induced activation of both potentially tumor-specific CD8⁺ T cells and T_REG cells, which were tightly associated with each other. These results may support the use of T_REG cell-modulating strategies with SBRT to improve the antitumor immune response.