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R/R DLBCL 患者中的肥胖和超重与 R2-GDP-GOTEL 试验治疗反应更好相关。NK CD8+细胞和维生素 D 的潜在作用

英文原题:Obesity and overweight in R/R DLBCL patients is associated with a better response to treatment of R2-GDP-GOTEL trial. Potential role of NK CD8 + cells and vitamin D.

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Obesity and overweight in R/R DLBCL patients is associated with a better response to treatment of R2-GDP-GOTEL trial. Potential role of NK CD8 + cells and vitamin D.

PubMed 2025/03/04(内容时间) Cancer Metab Q1 · IF 5.9(JCR 2025)

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研究概要

我们的研究结果表明,超重并不会加剧 DLBCL 的进展。相反,它似乎赋予了生存优势并改善了治疗反应,免疫系统可能在介导这些效应中发挥了关键作用。

研究思路结论见上方概要

弥漫大B细胞淋巴瘤(DLBCL)是全球最常见的非霍奇金淋巴瘤类型,其特征是异质性。尽管一线治疗改善了DLBCL患者的生存结局,但约三分之一患者会复发,且预后往往较差。在影响癌症患者(包括淋巴瘤患者)预后和治疗反应的因素中,超重和肥胖已成为重要的考量因素。然而,超重在DLBCL中的作用仍存在争议,研究报告了对癌症结局的负面和正面影响。在这项R2-GDP-GOTEL试验的转化子研究中,我们评估了超重作为复发/难治性(R/R)DLBCL患者治疗反应和生存预测因素的影响,并检查了其与免疫细胞动态的关系。

在II期试验中接受R2-GDP方案的79名患者中,有75名患者在开始治疗前获得了体重和身高参数。通过流式细胞术对血液样本进行了分析。进行了统计分析,以确定基线时超重和肥胖对R/R DLBCL患者的预后价值。

我们的结果表明,超重(包括肥胖)患者相比理想体重患者表现出更长的生存期。该组还显示出具有促肿瘤活性的调节性T细胞减少,以及具有抗肿瘤活性的自然杀伤(NK)样T细胞增加。此外,我们发现超重与更好的治疗反应相关,并与维生素D和CD8+ NK细胞水平升高相关。

展开英文摘要原文

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma worldwide and is characterized by its heterogeneity. Although first-line therapy improves survival outcomes for DLBCL patients, approximately one third will relapse, often with a poor prognosis. Among the factors influencing prognosis and response to treatment in cancer patients, including those with lymphoma, overweight and obesity have emerged as significant considerations. However, the role of excess weight in DLBCL remains controversial, with studies reporting both negative and positive effects on cancer outcomes. In this translational substudy of the R2-GDP-GOTEL trial, we have evaluated the impact of excess weight as a predictor of treatment response and survival in patients with relapsed/refractory (R/R) DLBCL, and examining its relationship with immune cell dynamics.

Of the 79 patients who received the R2-GDP scheme in the phase II trial, weight and height parameters were obtained in 75 patients before starting treatment. Blood samples were analyzed by flow cytometry. Statistical analyses were performed to determine the prognostic value of overweight and obesity at baseline in R/R DLBCL patients.

Our results indicate that overweight (including obese) patients exhibit longer survival compared to patients of ideal weight. This group also demonstrated a reduction of regulatory T cells with supposedly protumor activity and an increase of Natural Killer (NK)-like T cells with supposedly antitumor activity. Additionally, we have found that excess weight correlates with better treatment response, associated with elevated levels of vitamin D and CD8 + NK cells.

Our findings suggest that excess weight does not exacerbate the progression of DLBCL. Instead, it appears to confer a survival advantage and improve treatment response, with the immune system playing a possible pivotal role in mediating these effects. TRIAL REGISTRATION: EudraCT, ID:2014-001620-29.

论文信息

作者
Hontecillas-Prieto L、García-Domínguez DJ、Jiménez-Cortegana C、Nogales-Fernández E、Palazón-Carrión N、García-Sancho AM、Ríos-Herranz E、Gumà-Padrò J
第一作者单位
Clinical Biochemistry Service, Virgen Macarena University Hospital, University of Seville, Seville, Spain.Spain
通讯作者单位
Clinical Biochemistry Service, Virgen Macarena University Hospital, University of Seville, Seville, Spain. margalet@us.es.Spain
期刊
Cancer & metabolism2025 Mar 4
原文标识
PubMed 40038834 · DOI 10.1186/s40170-025-00381-7