该研究调查了接受免疫检查点抑制剂（ICIs）治疗的癌症患者的血清促炎细胞因子水平、胆固醇代谢和临床结果之间的关系。在治疗前从接受 ICI 治疗的晚期癌症患者身上采集外周血。我们回顾性评估了血浆总胆固醇 (TC)、ABCA1 和 ABCG1 介导的胆固醇流出 (CE)、被动扩散 (PD)、胆固醇负荷能力 (CLC) 以及血清 IL-6、IL-10 和 TNF-α。对血液胆固醇参数和炎症细胞因子之间的关联及其对总生存期 (OS)、无进展生存期 (PFS) 和 ICI 的临床获益 (CB) 的影响进行了统计评估。在70名连续入组的患者中（非小细胞肺癌：94%；肾细胞癌：6%），IL-6low和IL-10low病例中TC、CLC和胆固醇PD显着较高（P<0.05），而ABCA1- IL-10高的患者介导的CE增加（P=0.018）。单变量和多变量分析显示，IL-6low（HR 分别为 2.13 和 2.97）和 IL-10low（HR 3.17 和 2.62）组的 OS 和 PFS 显着延长。在单变量分析中，所有胆固醇相关指数与 OS 和 PFS 显着相关，而在多变量分析中，仅高 PD 被验证为保护因素（OS，HR 0.75；PFS，HR 0.84）。最后，单变量和多变量显示 CB 与 ABCG1-CE (OR 0.62)、IL-6 (OR 0.13) 和 IL-10 (OR 0.10) 呈统计学显着负相关。深入表征血液胆固醇代谢和免疫炎症细胞因子之间的相互作用可能会为癌症、炎症、血脂谱和免疫治疗反应之间的复杂关系提供新的见解。版权所有 © 2024 Wolters Kluwer Health, Inc. 保留所有权利。

The study investigated the relationship between serum proinflammatory cytokine levels, cholesterol metabolism, and clinical outcome in cancer patients undergoing immune checkpoint inhibitors (ICIs). Peripheral blood was collected before therapy from ICI-treated advanced cancer patients. We retrospectively assessed plasma total cholesterol (TC), ABCA1- and ABCG1-mediated cholesterol efflux (CE), passive diffusion (PD), cholesterol loading capacity (CLC), and serum IL-6, IL-10, and TNF-α. The association between blood cholesterol parameters and inflammatory cytokines and their effect on overall survival (OS), progression-free survival (PFS), and clinical benefit (CB) from ICIs were statistically assessed. Among 70 consecutively enrolled patients (nonsmall cell lung cancer: 94%; renal cell carcinoma: 6%), TC, CLC, and cholesterol PD resulted significantly higher in IL-6low and IL-10low cases (P<0.05), whereas ABCA1-mediated CE was increased in IL-10high patients (P=0.018). Uni- and multivariable analysis revealed meaningfully longer OS and PFS in IL-6low (HR 2.13 and 2.97, respectively) and IL-10low (HR 3.17 and 2.62) groups. At univariate analysis all cholesterol-related indices significantly correlated with OS and PFS, whereas at multivariate only high PD was validated as a protection factor (OS, HR 0.75; PFS, HR 0.84). Finally, uni- and multivariable showed a statistically significant inverse association of CB with ABCG1-CE (OR 0.62), as with IL-6 (OR 0.13) and IL-10 (OR 0.10). In-depth characterization of the interplay between blood cholesterol metabolism and immune-inflammatory cytokines might provide novel insights into the complex relationship among cancer, inflammation, lipids profile, and response to immunotherapy.Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.