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Clin Genitourin Cancer. 2018 Apr;16(2):e469-e476. doi: 10.1016/j.clgc.2017.10.010. Epub 2017 Oct 24.

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

Author information

1
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT; Prostate and Urological Cancers Program, Yale Comprehensive Cancer Center, New Haven, CT. Electronic address: joseph.w.kim@yale.edu.
2
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
3
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT; Prostate and Urological Cancers Program, Yale Comprehensive Cancer Center, New Haven, CT.

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.

KEYWORDS:

Immune effect; PD-1; Radioisotope; Survival; Xofigo

PMID:
29137877
PMCID:
PMC5878980
DOI:
10.1016/j.clgc.2017.10.010
[Indexed for MEDLINE]
Free PMC Article

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