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

BACKGROUND

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.

Informations de copyright

Copyright © 2021 Creemers, van der Doelen, van Wilpe, Hermsen, Duiveman-de Boer, Somford, Janssen, Sedelaar, Mehra, Textor and Westdorp.

Déclaration de conflit d'intérêts

MD received research grants form Bayer (to institution) during the conduct of the study, travel expenses from Bayer, research grants from Janssen Pharmaceuticals, and personal fees from Astellas outside the submitted work. RH is member of the advisory board of Bayer, and received personal fees and travel expenses from Bayer outside the submitted work. DS is a member of the advisory boards of Janssen Pharmaceuticals, Astellas and Bayer, and received research grants from Astellas outside the submitted work. NM is a member of the advisory boards of Bayer, Bristol Myers Squibb, Roche, Merck Sharp and Dome, Astellas and Janssen Pharmaceuticals, and reports personal fees from Bayer, research grants and personal fees from Janssen Pharmaceuticals, Merck Sharp and Dohme, Roche, Astellas, AstraZeneca and Sanofi, and research grants from Pfizer and Genzyme outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.