Association between the Immunophenotype of Peripheral Blood from mCRPC Patients and the Outcomes of Radium-223 Treatment

Author:

Cantó Elisabet1,Anguera Georgia2,Jiménez Natalia3ORCID,Mellado Begoña4ORCID,Ramírez Ona5,Mariscal Anais6ORCID,Maroto Pablo2,Vidal Silvia1ORCID

Affiliation:

1. Inflammatory Diseases, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain

2. Department of Medical Oncology, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, 08025 Barcelona, Spain

3. Translational Genomics and Targeted Therapeutics in Solid Tumors Laboratory, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain

4. Medical Oncology Department, Hospital Clinic Institut d’Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain

5. Medical Oncology Department, Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain

6. Immunology Department, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), 08041 Barcelona, Spain

Abstract

(1) Background: Prostate cancer is the second most common cancer in men, with androgen suppression as the standard treatment. Despite initially responding to castration, most metastatic prostate cancer patients eventually experience progression. In these cases, Radium-223 is the chosen treatment. We hypothesized that the immunophenotype of circulating leukocytes conditions the response to Radium-223 treatment. (2) Material and Methods: In this prospective study, we collected peripheral blood from twelve mCRPC patients and nine healthy donors before (baseline) and during treatment with Radium-223. Immunophenotyping and the percentages of leukocyte–platelet complexes were determined by flow cytometry. The increments or decrements of leukocyte subsets between the baseline and the second Radium-223 injection were also calculated. (3) Results: At baseline, the mCRPC patients had a lower percentages of CD4+ T cells and B cells and higher percentages of NK and neutrophils than the HDs. In addition, they had more OX40+ CD4+ T cells, PD-L1+ CD8low cells, PD-L1+ B cells, PD-L1+ NK cells, and monocyte–platelet complexes than the HDs. Moreover, patients with slow and fast progression had different percentages of PD-L1+ CD8+ T cells. In particular, slow progression patients underwent an increment of PD-L1+ CD8+ T cells after two cycles of Radium-223. (4) Conclusions: The characterization of circulating immune cells before initiating Radium-223 treatment could become a non-invasive indicator of the response.

Funder

Bayer donation

Publisher

MDPI AG

Subject

Clinical Biochemistry

Reference34 articles.

1. Utilization and Outcomes of Surgical Castration in Comparison to Medical Castration in Metastatic Prostate Cancer;Garje;Clin. Genitourin. Cancer,2019

2. An update on androgen deprivation therapy for prostate cancer;Sharifi;Endocr. Relat. Cancer,2010

3. Alpha Emitter Radium-223 and Survival in Metastatic Prostate Cancer;Parker;N. Engl. J. Med.,2013

4. Radium 223 dichloride for prostate cancer treatment;Deshayes;Drug Des. Dev. Ther.,2017

5. Immune Analysis of Radium-223 in Patients With Metastatic Prostate Cancer. Clin. Genitourin;Kim;Cancer,2018

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