Immune Analysis of Radium-223 in Patients With Metastatic Prostate Cancer

Abstract Background Radium223 (Ra223) delivers high-energy radiation to osteoblastic metastasis of prostate cancer, resulting in irreparable double-stranded DNA damage. The effects of Ra223 on CD8+ T cell subsets in patients with prostate cancer is unknown. Patients and Methods Fifteen men with metastatic prostate cancer with clinical indication for Ra223 without any autoimmune or immune deficiency conditions were enrolled. Patients received a course of Ra223 50 kBq/kg. Concurrent use of prednisone ≤ 10 mg a day was allowed. Peripheral blood samples were collected before and 3 to 4 weeks after the first dose of Ra223 50 kBq/kg. Peripheral blood mononuclear cells were purified and analyzed for the phenotypic and functional characteristics of CD8 + T cells using flow cytometry. Results One Ra223 treatment did not result in significant change in the overall frequencies of CD8 + T cells and their subsets including naive, central memory, and effect memory cells. However, the mean frequency of programmed cell death protein 1-expressing EM CD8 + T cells decreased after 1 Ra223 treatment from 20.6% to 14.6% ( P  = .020), whereas no significant change was observed in the frequencies of CD27-, CD28-, or CTLA4-expressing T cells. One Ra223 treatment was not associated with any significant change in the frequencies of CD8 + T cells producing IFN-γ, TNF-α, and IL-13. Conclusion One Ra223 treatment is associated with a decreased mean frequency of programmed cell death protein 1-expressing effect memory CD8 + T cell without affecting other immune checkpoint molecules or cytokine production. Further investigations are warranted to elucidate the immunologic and clinical significance of our observations and its long-term effects after multiple treatments.