In:
Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-5-18)
Abstract:
Radium-223 improves overall survival (OS) in men with bone metastatic castration-resistant prostate cancer (mCRPC). While the exact mechanism behind this survival benefit remains unclear, radium-induced immunological mechanisms might contribute to the OS advantage. We performed a comprehensive evaluation of the immunological changes in mCRPC patients by phenotyping the peripheral blood mononuclear cells (PBMCs) during radium-223 therapy. Materials and Methods In this prospective, single-arm, exploratory study, PBMCs of 30 mCRPC patients were collected before, during, and after treatment with radium-223. Lymphocyte and monocyte counts were analyzed to get insight into general immune cell trends. Next, we analyzed changes in T cell subsets, myeloid-derived suppressor cells (MDSCs), and immune checkpoint expression using linear regression models. Per subset, the 6-month change (% of baseline) was determined. Bootstrapped 95% confidence intervals were used to measure the degree of uncertainty of our findings. Results We observed a substantial decrease in absolute lymphocyte counts (-0.12 * 10^9 cells/L per injection, 95% CI: -0.143 - -0.102). Simultaneously, an increase was observed in the proportion of T cells that expressed costimulatory (ICOS) or inhibitory (TIM-3, PD-L1, and PD-1) checkpoint molecules. Moreover, the fraction of two immunosuppressive subsets – the regulatory T cells and the monocytic MDSCs – increased throughout treatment. These findings were not more pronounced in patients with an alkaline phosphatase response during therapy. Conclusion Immune cell subsets in patients with mCRPC changed during radium-223 therapy, which warrants further research into the possible immunological consequences of these changes.
Type of Medium:
Online Resource
ISSN:
2234-943X
DOI:
10.3389/fonc.2021.667658
DOI:
10.3389/fonc.2021.667658.s001
DOI:
10.3389/fonc.2021.667658.s002
DOI:
10.3389/fonc.2021.667658.s003
DOI:
10.3389/fonc.2021.667658.s004
DOI:
10.3389/fonc.2021.667658.s005
DOI:
10.3389/fonc.2021.667658.s006
DOI:
10.3389/fonc.2021.667658.s007
DOI:
10.3389/fonc.2021.667658.s008
DOI:
10.3389/fonc.2021.667658.s009
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2021
detail.hit.zdb_id:
2649216-7
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