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

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; Enrique Gonzalez-Billalabeitia

doi:10.3390/cancers16142535

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

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 SantanderMaria 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, Enrique Gonzalez-Billalabeitia

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	2535
Journal	Cancers
Volume	16
Issue number	14
DOIs	https://doi.org/10.3390/cancers16142535
State	Published - Jul 2024
Externally published	Yes

Keywords

castration-resistant prostate cancer (CRPC)
enzalutamide
prognostic factors
prostate cancer
whole blood

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10.3390/cancers16142535

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Perez-Navarro, E., Conteduca, V., Funes, J. M., Dominguez, J. I., Martin-Serrano, M., Cremaschi, P., Fernandez-Perez, M. P., Gordoa, T. A., Font, A., Vázquez-Estévez, S., González-del-Alba, A., Wetterskog, D., Mellado, B., Fernandez-Calvo, O., Méndez-Vidal, M. J., Climent, M. A., Duran, I., Gallardo, E., Rodriguez Sanchez, A., ... Gonzalez-Billalabeitia, E. (2024). Prognostic Implications of Blood Immune-Cell Composition in Metastatic Castration-Resistant Prostate Cancer. Cancers, 16(14), Article 2535. https://doi.org/10.3390/cancers16142535

@article{72224c416b9b4d65b4af2b4135441528,

title = "Prognostic Implications of Blood Immune-Cell Composition in Metastatic Castration-Resistant Prostate Cancer",

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.",

keywords = "castration-resistant prostate cancer (CRPC), enzalutamide, prognostic factors, prostate cancer, whole blood",

author = "Enrique Perez-Navarro and Vincenza Conteduca and Funes, {Juan M.} and Dominguez, {Jose I.} and Miguel Martin-Serrano and Paolo Cremaschi and Fernandez-Perez, {Maria Piedad} and Gordoa, {Teresa Alonso} and Albert Font and Sergio V{\'a}zquez-Est{\'e}vez and Ar{\'a}nzazu Gonz{\'a}lez-del-Alba and Daniel Wetterskog and Begona Mellado and Ovidio Fernandez-Calvo and M{\'e}ndez-Vidal, {Mar{\'i}a Jos{\'e}} and Climent, {Miguel Angel} and Ignacio Duran and Enrique Gallardo and {Rodriguez Sanchez}, Angel and Carmen Santander and S{\'a}ez, {Maria Isabel} and Javier Puente and Julian Tudela and Cecilia Marinas and L{\'o}pez-Andreo, {Mar{\'i}a Jose} and Daniel Castellano and Gerhardt Attard and Enrique Grande and Antonio Rosino and Botia, {Juan A.} and Jose Palma-Mendez and {De Giorgi}, Ugo and Enrique Gonzalez-Billalabeitia",

note = "Publisher Copyright: {\textcopyright} 2024 by the authors.",

year = "2024",

month = jul,

doi = "10.3390/cancers16142535",

language = "English",

volume = "16",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "14",

}

Perez-Navarro, E, Conteduca, V, Funes, JM, Dominguez, JI, Martin-Serrano, M, Cremaschi, P, Fernandez-Perez, MP, Gordoa, TA, Font, A, Vázquez-Estévez, S, González-del-Alba, A, Wetterskog, D, Mellado, B, Fernandez-Calvo, O, Méndez-Vidal, MJ, Climent, MA, Duran, I, Gallardo, E, Rodriguez Sanchez, A, Santander, C, Sáez, MI, Puente, J, Tudela, J, Marinas, C, López-Andreo, MJ, Castellano, D, Attard, G, Grande, E, Rosino, A, Botia, JA, Palma-Mendez, J, De Giorgi, U & Gonzalez-Billalabeitia, E 2024, 'Prognostic Implications of Blood Immune-Cell Composition in Metastatic Castration-Resistant Prostate Cancer', Cancers, vol. 16, no. 14, 2535. https://doi.org/10.3390/cancers16142535

TY - JOUR

T1 - Prognostic Implications of Blood Immune-Cell Composition in Metastatic Castration-Resistant Prostate Cancer

AU - Perez-Navarro, Enrique

AU - Conteduca, Vincenza

AU - Funes, Juan M.

AU - Dominguez, Jose I.

AU - Martin-Serrano, Miguel

AU - Cremaschi, Paolo

AU - Fernandez-Perez, Maria Piedad

AU - Gordoa, Teresa Alonso

AU - Font, Albert

AU - Vázquez-Estévez, Sergio

AU - González-del-Alba, Aránzazu

AU - Wetterskog, Daniel

AU - Mellado, Begona

AU - Fernandez-Calvo, Ovidio

AU - Méndez-Vidal, María José

AU - Climent, Miguel Angel

AU - Duran, Ignacio

AU - Gallardo, Enrique

AU - Rodriguez Sanchez, Angel

AU - Santander, Carmen

AU - Sáez, Maria Isabel

AU - Puente, Javier

AU - Tudela, Julian

AU - Marinas, Cecilia

AU - López-Andreo, María Jose

AU - Castellano, Daniel

AU - Attard, Gerhardt

AU - Grande, Enrique

AU - Rosino, Antonio

AU - Botia, Juan A.

AU - Palma-Mendez, Jose

AU - De Giorgi, Ugo

AU - Gonzalez-Billalabeitia, Enrique

PY - 2024/7

Y1 - 2024/7

N2 - 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.

AB - 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.

KW - castration-resistant prostate cancer (CRPC)

KW - enzalutamide

KW - prognostic factors

KW - prostate cancer

KW - whole blood

UR - http://www.scopus.com/inward/record.url?scp=85199659554&partnerID=8YFLogxK

U2 - 10.3390/cancers16142535

DO - 10.3390/cancers16142535

M3 - Article

AN - SCOPUS:85199659554

SN - 2072-6694

VL - 16

JO - Cancers

JF - Cancers

IS - 14

M1 - 2535

ER -

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

Abstract

Keywords

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