e1388e380d18ae7dfc61ec8591ddb224 299783.pdf 949c9f6fcefba584d391e3e555c6f61153a6c319 299783.pdf f4beb461504ad88e0b2a3b916c2aa552a6aa5c75fae2ba592a85d30fba190d5f 299783.pdf Title: Prognostic Implications of Blood Immune-Cell Composition in Metastatic Castration-Resistant Prostate Cancer Subject: The prognosis for patients with metastatic castration-resistant prostate cancer (mCRPC) varies, being influenced by blood-related factors such as transcriptional profiling and immune cell ratios. We aimed to address the contribution of distinct whole blood immune cell components to the prognosis of these patients. This study analyzed pre-treatment blood samples from 152 chemotherapy-naive mCRPC patients participating in a phase 2 clinical trial (NCT02288936) and a validation cohort. We used CIBERSORT-X to quantify 22 immune cell types and assessed their prognostic significance using Kaplan–Meier and Cox regression analyses. Reduced CD8 T-cell proportions and elevated monocyte levels were substantially connected with a worse survival. High monocyte counts correlated with a median survival of 32.2 months versus 40.3 months for lower counts (HR: 1.96, 95% CI 1.11–3.45). Low CD8 T-cell levels were associated with a median survival of 31.8 months compared to 40.3 months for higher levels (HR: 1.97, 95% CI 1.11–3.5). These findings were consistent in both the trial and validation cohorts. Multivariate analysis further confirmed the independent prognostic value of CD8 T-cell counts. This study highlights the prognostic implications of specific blood immune cells, suggesting they could serve as biomarkers in mCRPC patient management and should be further explored in clinical trials. Keywords: prostate cancer; castration-resistant prostate cancer (CRPC); enzalutamide; whole blood; prognostic factors Author: Enrique Perez-Navarro, Vincenza Conteduca, Juan M. Funes, Jose I. Dominguez, Miguel Martin-Serrano, Paolo Cremaschi, Maria Piedad Fernandez-Perez, Teresa Alonso Gordoa, Albert Font, Sergio Vázquez-Estévez, Aránzazu González-del-Alba, Daniel Wetterskog, Begona Mellado, Ovidio Fernandez-Calvo, María José Méndez-Vidal, Miguel Angel Climent, Ignacio Duran, Enrique Gallardo, Angel Rodriguez Sanchez, Carmen Santander, Maria Isabel Sáez, Javier Puente, Julian Tudela, Cecilia Marinas, María Jose López-Andreo, Daniel Castellano, Gerhardt Attard, Enrique Grande, Antonio Rosino, Juan A. Botia, Jose Palma-Mendez, Ugo De Giorgi and Enrique Gonzalez-Billalabeitia Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Sun Jul 14 10:55:53 2024 CEST ModDate: Sun Jul 14 10:58:14 2024 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: 1507020 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- JYPLJJ+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 PKEZZB+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 UHKRUI+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 SXRJZS+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 GFKJOY+VnURWPalladioL Type 1 Custom yes yes yes 32 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 49 0 OQIVQT+EURM10 Type 1 Builtin yes yes yes 69 0 UFKNXE+CMSY10 Type 1 Builtin yes yes yes 74 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 90 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 94 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 98 0 BCDHEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 102 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 108 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 114 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 126 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 130 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 134 0 BCDHEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 138 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 144 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 150 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 162 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 171 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 175 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 179 0 BCDHEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 183 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 189 0 BCDJEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 195 0 BCDKEE+PalatinoLinotype-BoldItalic CID TrueType Identity-H yes yes yes 201 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-09-03 02:37:30 CEST RepresentationInformation: 299783.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-09-02 13:48:10 CEST Size: 1507020 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 361 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: Study Design and Conduct Destination: subsection.2.1 Item: Title: Sample Collection Destination: subsection.2.2 Item: Title: RNA Extraction and Microarray Analysis Destination: subsection.2.3 Item: Title: Gene Expression Analysis Destination: subsection.2.4 Item: Title: CTC and AR-V7 Analysis Destination: subsection.2.5 Item: Title: Statistical Analysis Destination: subsection.2.6 Item: Title: Results Destination: section.3 Children: Item: Title: Study Population Destination: subsection.3.1 Item: Title: Blood Immune-Cell Composition Destination: subsection.3.2 Item: Title: Prognostic Significance of Individual Immune Cell Types Destination: subsection.3.3 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Prognostic Implications of Blood Immune-Cell Composition in Metastatic Castration-Resistant Prostate Cancer Author: Enrique Perez-Navarro, Vincenza Conteduca, Juan M. Funes, Jose I. Dominguez, Miguel Martin-Serrano, Paolo Cremaschi, Maria Piedad Fernandez-Perez, Teresa Alonso Gordoa, Albert Font, Sergio Vázquez-Estévez, Aránzazu González-del-Alba, Daniel Wetterskog, Begona Mellado, Ovidio Fernandez-Calvo, María José Méndez-Vidal, Miguel Angel Climent, Ignacio Duran, Enrique Gallardo, Angel Rodriguez Sanchez, Carmen Santander, Maria Isabel Sáez, Javier Puente, Julian Tudela, Cecilia Marinas, María Jose López-Andreo, Daniel Castellano, Gerhardt Attard, Enrique Grande, Antonio Rosino, Juan A. Botia, Jose Palma-Mendez, Ugo De Giorgi and Enrique Gonzalez-Billalabeitia Subject: The prognosis for patients with metastatic castration-resistant prostate cancer (mCRPC) varies, being influenced by blood-related factors such as transcriptional profiling and immune cell ratios. We aimed to address the contribution of distinct whole blood immune cell components to the prognosis of these patients. This study analyzed pre-treatment blood samples from 152 chemotherapy-naive mCRPC patients participating in a phase 2 clinical trial (NCT02288936) and a validation cohort. We used CIBERSORT-X to quantify 22 immune cell types and assessed their prognostic significance using Kaplan Meier and Cox regression analyses. Reduced CD8 T-cell proportions and elevated monocyte levels were substantially connected with a worse survival. High monocyte counts correlated with a median survival of 32.2 months versus 40.3 months for lower counts (HR: 1.96, 95% CI 1.11 3.45). Low CD8 T-cell levels were associated with a median survival of 31.8 months compared to 40.3 months for higher levels (HR: 1.97, 95% CI 1.11 3.5). These findings were consistent in both the trial and validation cohorts. Multivariate analysis further confirmed the independent prognostic value of CD8 T-cell counts. This study highlights the prognostic implications of specific blood immune cells, suggesting they could serve as biomarkers in mCRPC patient management and should be further explored in clinical trials. 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