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Abstract
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 (TREG) 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 TREG cells were also activated after SBRT; this pattern was also evident among effector Foxp3hiCD45RA- TREG cells. We observed no difference in T-cell responses according to the fraction size and number. Notably, activation of TREG 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 TREG 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 TREG cells, which were tightly associated with each other. These results may support the use of TREG cell-modulating strategies with SBRT to improve the antitumor immune response.

Affiliations

Seung Hyuck Jeon 1, Bum-Sup Jang 2, Dong-Yun Kim 2, Jin Ho Kim 3, Eui-Cheol Shin 4, In Ah Kim 5
1Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
2Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
3Department of Radiation Oncology, Seoul National University Hospital, Seoul, Republic of Korea; Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea.
4Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea; The Center for Viral Immunology, Korea Virus Research Institute, Institute for Basic Science (IBS), Daejeon, Republic of Korea. Electronic address: ecshin@kaist.ac.kr.
5Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea; Medical Science Research Institute, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; Department of Tumor Biology and Cancer Research Institute, Seoul National University, Seoul, Republic of Korea; Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea. Electronic address: inah228@snu.ac.kr.