0b296d539ee473155849b10cf24c5498 pmc_10340498.pdf a41f877cefec926a00eeef172ffeb4207b708943 pmc_10340498.pdf eab08f1f296854a35f05e550d81438ffe9d5e504ebc2a5383743b019a7916f71 pmc_10340498.pdf Title: Association between the Immunophenotype of Peripheral Blood from mCRPC Patients and the Outcomesof Radium-223 Treatment Subject: (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. Keywords: metastatic prostate cancer; radium-223; immunophenotype Author: Elisabet Cantó, Georgia Anguera, Natalia Jiménez, Begoña Mellado, Ona Ramírez, Anais Mariscal, Pablo Maroto and Silvia Vidal Creator: LaTeX with hyperref Producer: MiKTeX pdfTeX-1.40.21 CreationDate: Thu Jun 29 15:05:19 2023 CEST ModDate: Thu Jun 29 15:11:16 2023 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1030427 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- JJNJIA+VnURWPalladioL Type 1 Custom yes yes no 10 0 LBBNDO+URWPalladioL-Bold Type 1 Custom yes yes no 15 0 GOLZGC+URWPalladioL-Roma Type 1 Custom yes yes no 20 0 CKUTBS+URWPalladioL-Ital Type 1 Custom yes yes no 24 0 XWOCXD+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 BXZUUH+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 46 0 CZMDWU+CMSY10 Type 1 Builtin yes yes no 68 0 OVNEXW+EURM10 Type 1 Builtin yes yes no 72 0 XIRVNA+EURB10 Type 1 Builtin yes yes no 82 0 URYLRZ+URWPalladioL-BoldItal Type 1 Custom yes yes no 86 0 OKIJHL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 109 0 OKIJHM+PalatinoLinotype CID TrueType Identity-H yes yes yes 112 0 OKIJHN+PalatinoLinotype TrueType WinAnsi yes yes no 118 0 OKIJHP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 121 0 OKIJHL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 141 0 OKIJHM+PalatinoLinotype CID TrueType Identity-H yes yes yes 144 0 OKIJHN+PalatinoLinotype TrueType WinAnsi yes yes no 150 0 OKIJHP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 153 0 OKIJHL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 172 0 OKIJHN+PalatinoLinotype TrueType WinAnsi yes yes no 175 0 OKIJHP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 178 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-04-25 02:43:21 CEST RepresentationInformation: pmc_10340498.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-04-24 02:40:39 CEST Size: 1030427 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 322 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Patient’s Samples Destination: subsection.2.1 Item: Title: Flow Cytometry Destination: subsection.2.2 Item: Title: Statistical Analysis Destination: subsection.2.3 Item: Title: Results Destination: section.3 Children: Item: Title: Demographic and Clinical Characteristics of mCRPC Patients at Baseline Destination: subsection.3.1 Item: Title: Baseline Expression of Immunomodulatory Molecules on Leukocytesand Leukocyte Platelet Complexes Destination: subsection.3.2 Item: Title: Relationship between Baseline Blood Immune Subpopulations, Leukocyte Platelet Complexes and the Clinic Characteristics of mCRPC Patients Destination: subsection.3.3 Item: Title: Circulating PD-L1+ CD8+ T Cells at Baseline Were Associated with Progression-Free Survival in mCRPC Patients Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Item: Title: References Destination: section.A. Info: Title: Association between the Immunophenotype of Peripheral Blood from mCRPC Patients and the Outcomesof Radium-223 Treatment Author: Elisabet Cantó, Georgia Anguera, Natalia Jiménez, Begoña Mellado, Ona Ramírez, Anais Mariscal, Pablo Maroto and Silvia Vidal Subject: (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. 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