دورية أكاديمية
Immunophenotyping Reveals Longitudinal Changes in Circulating Immune Cells During Radium-223 Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer
| العنوان: | Immunophenotyping Reveals Longitudinal Changes in Circulating Immune Cells During Radium-223 Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer |
|---|---|
| المؤلفون: | 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 |
| المصدر: | Frontiers in Oncology, Vol 11 (2021) |
| بيانات النشر: | Frontiers Media S.A., 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | metastatic castration-resistant prostate cancer (mCRPC), immune checkpoints, radionuclide therapy, radium-223, immunophenotyping, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | BackgroundRadium-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 MethodsIn 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.ResultsWe 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.ConclusionImmune cell subsets in patients with mCRPC changed during radium-223 therapy, which warrants further research into the possible immunological consequences of these changes. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2234-943X |
| العلاقة: | https://www.frontiersin.org/articles/10.3389/fonc.2021.667658/fullTest; https://doaj.org/toc/2234-943XTest |
| DOI: | 10.3389/fonc.2021.667658 |
| الوصول الحر: | https://doaj.org/article/9681b271f3804ad081b66ebff52e0e79Test |
| رقم الانضمام: | edsdoj.9681b271f3804ad081b66ebff52e0e79 |
| قاعدة البيانات: | Directory of Open Access Journals |
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