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可溶性肿瘤免疫组学特征预测癌症患者对强化免疫营养的肌肉量反应:一项多中心随机临床试验的亚分析

Soluble Oncoimmunome Signatures Predict Muscle Mass Response to Enriched Immunonutrition in Cancer Patients: Subanalysis of a Multicenter Randomized Clinical Trial.

作者信息

Cuesta-Sancho Sara, Gomez Juan José López, García-Luna Pedro Pablo, Primo David, Martínez-Ortega Antonio J, Izaola Olatz, Casañas Tamara, Calleja Alicia, Bernardo David, de Luis Daniel

机构信息

Mucosal Immunology Lab, Department of Paediatrics and Immunology, University of Valladolid, 47003 Valladolid, Spain.

Health Research Institute of Valladolid (IBioVALL), 47010 Valladolid, Spain.

出版信息

Nutrients. 2025 Jul 24;17(15):2421. doi: 10.3390/nu17152421.

DOI:10.3390/nu17152421
PMID:40806007
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12348936/
Abstract

BACKGROUND/OBJECTIVES: Enriched oral nutritional supplementation (ONS) has been shown to increase muscle mass in cancer patients. This study aims to identify the immunomodulatory effects and predictive biomarkers associated with this intervention.

METHODS

The soluble levels of 92 immune- and oncology-related mediators were determined before and after an intervention (8 weeks) in 28 patients with cancer receiving either a standard (n = 14) or an enriched ONS (n = 14) using the Olink proteomics analysis pipeline (Olink Target 96 Immuno-Oncology panel (Uppsala, Sweden)) Results: Patients receiving enriched ONS experienced an average weight gain of 1.4 kg and a muscle mass increase of 2.2 kg after 8 weeks, both statistically significant ( < 0.05), while no such improvements were observed in the standard ONS group. Inflammatory markers TRAIL and LAMP3 were significantly reduced, along with an increase in Gal-1, suggesting lower inflammation and enhanced myogenic differentiation. However, patients who failed to gain muscle mass with the enriched formula showed a more aggressive inflammatory profile, characterized by higher serum levels of soluble MUC16, ARG, and IL12RB1. Interestingly, muscle mass gain could be predicted before the intervention, as responders had lower baseline levels of PGF, CD28, and IL12RB1. These differences were specific to recipients of the enriched ONS, confirming its immunomodulatory effects.

CONCLUSIONS

Our findings support the use of enriched oral nutritional supplementation (ONS) as an effective strategy not only to enhance caloric and protein intake but also to promote anabolism and preserve muscle mass in cancer patients. The identification of immune profiles suggests that specific biomarkers could be used to predict which patients will benefit most from this type of intervention. This may allow for the implementation of personalized immunonutrition strategies that optimize resource allocation and improve clinical outcomes, particularly in vulnerable populations at risk of cachexia.

摘要

背景/目的:强化口服营养补充剂(ONS)已被证明可增加癌症患者的肌肉量。本研究旨在确定与该干预措施相关的免疫调节作用和预测生物标志物。

方法

使用Olink蛋白质组学分析流程(Olink Target 96免疫肿瘤学检测板(瑞典乌普萨拉)),测定了28例接受标准ONS(n = 14)或强化ONS(n = 14)的癌症患者在干预(8周)前后92种免疫和肿瘤相关介质的可溶性水平。结果:接受强化ONS的患者在8周后平均体重增加1.4kg,肌肉量增加2.2kg,两者均具有统计学意义(P < 0.05),而标准ONS组未观察到此类改善。炎症标志物TRAIL和LAMP3显著降低,同时Gal-1增加,提示炎症减轻和肌源性分化增强。然而,使用强化配方未能增加肌肉量的患者表现出更具侵袭性的炎症特征,其特点是血清可溶性MUC16、ARG和IL12RB1水平较高。有趣的是,在干预前就可以预测肌肉量的增加,因为反应者的PGF、CD28和IL12RB1基线水平较低。这些差异是强化ONS接受者所特有的,证实了其免疫调节作用。

结论

我们的研究结果支持使用强化口服营养补充剂(ONS)作为一种有效策略,不仅可以增加热量和蛋白质摄入,还可以促进合成代谢并维持癌症患者的肌肉量。免疫谱的确定表明,特定的生物标志物可用于预测哪些患者将从这类干预措施中获益最多。这可能有助于实施个性化免疫营养策略,优化资源分配并改善临床结果,特别是在有恶病质风险的脆弱人群中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1790/12348936/eefe36d85639/nutrients-17-02421-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1790/12348936/eefe36d85639/nutrients-17-02421-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1790/12348936/eefe36d85639/nutrients-17-02421-g003.jpg

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