A multidimensional analysis of the impact of obesity on immune checkpoint inhibitor therapy efficacy.

IF 5.3 2区医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2024-10-29 DOI:10.1186/s12935-024-03532-w

Wenjing Xu, Yifan Yang, Yue Yu, Lu Wu, Dong Ma, Rongrong Li, Lu Yang, Hengwen Sun

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Abstract

Background: Obesity is a well-known risk factor for developing malignant tumors and promoting tumor cell growth and spread. However, recent studies have shown that obese cancer patients, who typically have a worse prognosis than nonobese cancer patients, show a significant improvement in survival after receiving immune checkpoint inhibitor (ICI) therapy. This phenomenon is known as the "obesity paradox". However, this phenomenon is influenced by tumor type and sex. Therefore, this study aimed to explore the impact of obesity on immunotherapy efficacy from multiple perspectives, aiming to verify this paradox and provide new scientific evidence on the effect of obesity on ICI efficacy.

Methods: This retrospective study evaluated the data of patients who received ICI therapy between June 2019 and August 2023. Automatic segmentation of skeletal muscle, subcutaneous fat, and visceral fat was performed using Slice-O-Matic software, and the corresponding skeletal muscle index (SMI), subcutaneous fat index (SFI) and visceral fat index (VFI) were calculated. The neutrophil-to-lymphocyte ratio (NLR) was determined by dividing the neutrophil count by the lymphocyte count. Univariate and multivariate Cox regression analyses were used to evaluate the correlation between body mass index (BMI), body composition parameters, and the NLR with overall survival (OS) and progression-free survival (PFS) in obese patients receiving ICI therapy.

Results: We analyzed 219 patients with a median age of 60 years (IQR 53-69 years; 155 men and 64 women). Obese patients, particularly those with visceral fat accumulation, exhibited extended OS after ICI therapy (log-rank P = 0.027). Cox multivariate analysis revealed that the NLR (HR = 1.036; 95% CI: 0.996 to 1.078; P = 0.002) was independently associated with OS. Patients with a high NLR had worse OS than those with a low NLR.

Conclusions: This study corroborates the veracity of the "obesity paradox" under specific conditions and identifies NLR as an independent prognostic factor, with elevated NLR indicative of a poor prognosis.

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肥胖对免疫检查点抑制剂疗效影响的多维分析。

背景：众所周知，肥胖是罹患恶性肿瘤并促进肿瘤细胞生长和扩散的危险因素。然而，最近的研究表明，肥胖癌症患者的预后通常比非肥胖癌症患者更差，但在接受免疫检查点抑制剂（ICI）治疗后，肥胖癌症患者的生存率却显著提高。这一现象被称为 "肥胖悖论"。然而，这一现象受肿瘤类型和性别的影响。因此，本研究旨在从多个角度探讨肥胖对免疫疗法疗效的影响，旨在验证这一悖论，并为肥胖对ICI疗效的影响提供新的科学证据：这项回顾性研究评估了2019年6月至2023年8月期间接受ICI治疗的患者数据。使用 Slice-O-Matic 软件对骨骼肌、皮下脂肪和内脏脂肪进行了自动分割，并计算了相应的骨骼肌指数（SMI）、皮下脂肪指数（SFI）和内脏脂肪指数（VFI）。中性粒细胞与淋巴细胞比值（NLR）通过中性粒细胞计数除以淋巴细胞计数确定。采用单变量和多变量 Cox 回归分析评估接受 ICI 治疗的肥胖患者的体重指数（BMI）、身体成分参数和 NLR 与总生存期（OS）和无进展生存期（PFS）之间的相关性：我们对 219 名患者进行了分析，他们的中位年龄为 60 岁（IQR 53-69 岁；男性 155 人，女性 64 人）。肥胖患者，尤其是内脏脂肪堆积的患者，在接受 ICI 治疗后的 OS 延长（log-rank P = 0.027）。Cox多变量分析显示，NLR（HR = 1.036；95% CI：0.996 至 1.078；P = 0.002）与OS密切相关。与低NLR患者相比，高NLR患者的OS更差：本研究证实了特定条件下 "肥胖悖论 "的真实性，并确定NLR是一个独立的预后因素，NLR升高表明预后不良。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.