Immunophenotyping Reveals Longitudinal Changes in Circulating Immune Cells During Radium-223 Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer
| Autor: | 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 |
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| Rok vydání: | 2021 |
| Předmět: |
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 |
| Zdroj: | Frontiers in Oncology Frontiers in Oncology, 11, 1-10 Frontiers in Oncology, Vol 11 (2021) Frontiers in Oncology, 11, pp. 1-10 |
| ISSN: | 2234-943X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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