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 |
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| 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 Frontiers in Oncology, 11, 1-10 Frontiers in Oncology, Vol 11 (2021) Frontiers in Oncology, 11, pp. 1-10 |
| بيانات النشر: | Frontiers Media SA, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Oncology, Cancer Research, medicine.medical_specialty, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], radium-223, Lymphocyte, T cell, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], Peripheral blood mononuclear cell, Prostate cancer, All institutes and research themes of the Radboud University Medical Center, Immunophenotyping, Immune system, immunophenotyping, Internal medicine, Medicine, RC254-282, Original Research, business.industry, Monocyte, Data Science, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, radionuclide therapy, immune checkpoints, medicine.disease, Immune checkpoint, metastatic castration-resistant prostate cancer (mCRPC), medicine.anatomical_structure, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Radionuclide therapy, business |
| الوصف: | PurposeRadium-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.Experimental DesignIn 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 ALP 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. |
| وصف الملف: | application/pdf |
| تدمد: | 2234-943X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::49eeae0df2f328fef72818ddf671edd1Test https://doi.org/10.3389/fonc.2021.667658Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....49eeae0df2f328fef72818ddf671edd1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2234943X |
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