Immunophenotyping Reveals Longitudinal Changes in Circulating Immune Cells During Radium-223 Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer.

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.

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.

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.

Immune cell subsets in patients with mCRPC changed during radium-223 therapy, which warrants further research into the possible immunological consequences of these changes.

Frontiers in oncology. 2021 May 18*** epublish ***

Jeroen H A Creemers, Maarten J van der Doelen, Sandra van Wilpe, Rick Hermsen, Tjitske Duiveman-de Boer, Diederik M Somford, Marcel J R Janssen, J P Michiel Sedelaar, Niven Mehra, Johannes Textor, Harm Westdorp

Department of Tumor Immunology, Radboudumc, Nijmegen, Netherlands., Department of Medical Oncology, Radboudumc, Nijmegen, Netherlands., Department of Nuclear Medicine, Canisius-Wilhelmina Hospital, Nijmegen, Netherlands., Department of Urology, Canisius-Wilhelmina Hospital, Nijmegen, Netherlands., Department of Radiology and Nuclear Medicine, Radboudumc, Nijmegen, Netherlands., Department of Urology, Radboudumc, Nijmegen, Netherlands.

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