Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy.
Clin Lung Cancer. 2022 Nov;23(7):e489-e499. doi: 10.1016/j.cllc.2022.07.010. Epub 2022 Jul 21.
Lipid metabolism impacts immune cell differentiation, activation, and functions, modulating inflammatory mediators, energy homeostasis, and cell membrane composition. Despite preclinical evidence, data in humans lack concerning tumors and immunotherapy (IO). We aimed at investigating the correlations between circulating lipids and the outcome of non-small cell lung cancer (NSCLC) patients treated with IO.
We identified all patients with advanced NSCLC treated with IO at our Institution with available baseline plasma samples. Fatty acids (FAs) were analyzed through gas chromatography. Survival curves were estimated by the Kaplan-Meier method. Cox multivariate models were constructed through a stepwise procedure, with entry and exit P value set at .2.
We identified 112 patients, mostly with performance status 1 (65.2%) and PD-L1≥1% (75.3%). Median progression-free survival (PFS) and overall survival (OS) were 2.8 and 11.0 months, respectively. Multivariable model for survival identified a positive association of circulating free (FFA) C16:0 (P .005) and esterified (EFA) C16:1 (P .030) with PFS, and a positive association of EFA C16:1 (P .001) and EFA C18:0 (P .020) with OS. EFA C16:0 was negatively associated with PFS (P .008).
FFA C16:0 and FAs derived from its unsaturation (EFA C16:1) and elongation (EFA C18:0) are associated with a better outcome in NSCLC patients treated with IO. It is conceivable that the ratio among those FAs may modify membrane fluidity and receptor activity, influencing IO efficacy. These data pave the way for the investigation of lipid-modulating strategies in association with IO in NSCLC.
脂质代谢影响免疫细胞的分化、激活和功能，调节炎症介质、能量稳态和细胞膜组成。尽管有临床前证据，但人类在肿瘤和免疫治疗（IO）方面的数据仍缺乏。我们旨在研究循环脂质与接受 IO 治疗的非小细胞肺癌（NSCLC）患者结局之间的相关性。
我们在本机构确定了所有接受 IO 治疗的晚期 NSCLC 患者，并获得了基线血浆样本。通过气相色谱法分析脂肪酸（FA）。通过 Kaplan-Meier 方法估计生存曲线。通过逐步程序构建 Cox 多变量模型，进入和退出 P 值设置为.2。
我们确定了 112 名患者，主要表现为状态 1（65.2%）和 PD-L1≥1%（75.3%）。中位无进展生存期（PFS）和总生存期（OS）分别为 2.8 个月和 11.0 个月。生存的多变量模型确定循环游离（FFA）C16：0（P.005）和酯化（EFA）C16：1（P.030）与 PFS 呈正相关，EFA C16：1（P.001）和 EFA C18：0（P.020）与 OS 呈正相关。EFA C16：0 与 PFS 呈负相关（P.008）。
FFA C16：0 和源自其不饱和性（EFA C16：1）和延伸性（EFA C18：0）的 FAs 与接受 IO 治疗的 NSCLC 患者的更好结局相关。可以想象，这些 FA 之间的比率可能会改变膜的流动性和受体活性，从而影响 IO 的疗效。这些数据为在 NSCLC 中与 IO 联合进行脂质调节策略的研究铺平了道路。
