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转移性去势抵抗性前列腺癌血液免疫细胞组成的预后意义

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

作者信息

Perez-Navarro Enrique, Conteduca Vincenza, Funes Juan M, Dominguez Jose I, Martin-Serrano Miguel, Cremaschi Paolo, Fernandez-Perez Maria Piedad, Gordoa Teresa Alonso, Font Albert, Vázquez-Estévez Sergio, González-Del-Alba Aránzazu, Wetterskog Daniel, Mellado Begona, Fernandez-Calvo Ovidio, Méndez-Vidal María José, Climent Miguel Angel, Duran Ignacio, Gallardo Enrique, Rodriguez Sanchez Angel, Santander Carmen, Sáez Maria Isabel, Puente Javier, Tudela Julian, Marinas Cecilia, López-Andreo María Jose, Castellano Daniel, Attard Gerhardt, Grande Enrique, Rosino Antonio, Botia Juan A, Palma-Mendez Jose, De Giorgi Ugo, Gonzalez-Billalabeitia Enrique

机构信息

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

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

出版信息

Cancers (Basel). 2024 Jul 14;16(14):2535. doi: 10.3390/cancers16142535.

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.

摘要

转移性去势抵抗性前列腺癌(mCRPC)患者的预后各不相同,受到转录谱和免疫细胞比率等血液相关因素的影响。我们旨在探讨不同全血免疫细胞成分对这些患者预后的影响。本研究分析了参与一项2期临床试验(NCT02288936)的152例未经化疗的mCRPC患者的治疗前血样以及一个验证队列。我们使用CIBERSORT-X对22种免疫细胞类型进行定量,并通过Kaplan-Meier和Cox回归分析评估它们的预后意义。CD8 T细胞比例降低和单核细胞水平升高与较差的生存率密切相关。单核细胞计数高与中位生存期32.2个月相关,而计数低者为40.3个月(HR:1.96,95%CI 1.11-3.45)。低CD8 T细胞水平与中位生存期31.8个月相关,而水平高者为40.3个月(HR:1.97,95%CI 1.11-3.5)。这些发现在试验队列和验证队列中均一致。多变量分析进一步证实了CD8 T细胞计数的独立预后价值。本研究强调了特定血液免疫细胞的预后意义,表明它们可作为mCRPC患者管理中的生物标志物,应在临床试验中进一步探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1944/11274568/c5eb70163140/cancers-16-02535-g001.jpg

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