Prognostic Implications of Blood Immune-Cell Composition in Metastatic Castration-Resistant Prostate Cancer

Author:

Perez-Navarro Enrique12ORCID,Conteduca Vincenza3,Funes Juan M.1ORCID,Dominguez Jose I.1,Martin-Serrano Miguel1ORCID,Cremaschi Paolo4,Fernandez-Perez Maria Piedad5,Gordoa Teresa Alonso6,Font Albert7,Vázquez-Estévez Sergio8,González-del-Alba Aránzazu9ORCID,Wetterskog Daniel4,Mellado Begona10,Fernandez-Calvo Ovidio11ORCID,Méndez-Vidal María José12,Climent Miguel Angel13,Duran Ignacio14,Gallardo Enrique15ORCID,Rodriguez Sanchez Angel16,Santander Carmen17,Sáez Maria Isabel18,Puente Javier19,Tudela Julian20,Marinas Cecilia1,López-Andreo María Jose21ORCID,Castellano Daniel1,Attard Gerhardt4,Grande Enrique22ORCID,Rosino Antonio23ORCID,Botia Juan A.2,Palma-Mendez Jose2,De Giorgi Ugo24ORCID,Gonzalez-Billalabeitia Enrique125

Affiliation:

1. Department of Medical Oncology, Instituto de Investigación Imas12, Hospital Universitario 12 de Octubre, 28041 Madrid, Spain

2. Departamento de Ingeniería de la Información y las Comunicaciones, Universidad de Murcia, 30100 Murcia, Spain

3. Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy

4. University College London Cancer Institute, London WC1E 6DD, UK

5. Department of Haematology and Medical Oncology, Hospital Universitario Morales Meseguer, Instituto Murciano de Investigaciones Biosanitarias (IMIB), 30005 Murcia, Spain

6. Medical Oncology Department, Hospital Universitario Ramón y Cajal, 28034 Madrid, Spain

7. Institut Català dOncologia, Hospital Universitari Germans Trias i Pujol, 08029 Badalona, Spain

8. Hospital Universitario Lucus Augusti, 27003 Lugo, Spain

9. Medical Oncology Department, Hospital Universitario Puerta de Hierro-Majadahonda, 28222 Madrid, Spain

10. Medical Oncology Department, Hospital Clínic, 08036 Barcelona, Spain

11. Department of Medical Oncology, Complejo Hospitalario Universitario Ourense, 32005 Orense, Spain

12. Medical Oncology Department, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Hospital Universitario Reina Sofía, 14004 Córdoba, Spain

13. Instituto Valenciano de Oncología, 46009 Valencia, Spain

14. Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Valdecilla (IDIVAL), 39011 Santander, Spain

15. Medical Oncology Service, Parc Taulí Hospital Universitari, Institut d’Investigació i Innovació Parc Taulí I3PT, Universitat Autònoma de Barcelona, 08208 Sabadell, Spain

16. Department of Medical Oncology, University Hospital of León, 24071 León, Spain

17. Department of Medical Oncology, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain

18. UGCI Oncología Médica, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain

19. Medical Oncology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), CIBERONC, 28040 Madrid, Spain

20. Department of Pathology, Hospital Morales Meseguer, 30008 Murcia, Spain

21. Department of Molecular Biology, Servicio de Apoyo a la Investigación-Instituto Murciano de Investigación Biosanitaria (SAI-IMIB), Universidad de Murcia, 30100 Murcia, Spain

22. Medical Oncology Department, MD Anderson Cancer Center Madrid, Universidad Francisco de Vitoria, 28223 Madrid, Spain

23. Urology Department, Hospital Universitario Morales Meseguer, 30005 Murcia, Spain

24. IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, 47014 Meldola, Italy

25. Facultad de Medicina, Universidad Católica San Antonio de Murcia (UCAM), 30107 Murcia, Spain

Abstract

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.

Funder

Astellas

Instituto de Salud Carlos III

SEOM-CRIS cancer foundation

FERO Foundation

Publisher

MDPI AG

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