Intersecting Blood Cytokines With Cholesterol Parameters to Profile Patients With Advanced Solid Tumors Receiving Immune Checkpoint Inhibitors.
Journal
Journal of immunotherapy (Hagerstown, Md. : 1997)
ISSN: 1537-4513
Titre abrégé: J Immunother
Pays: United States
ID NLM: 9706083
Informations de publication
Date de publication:
11 Jul 2024
11 Jul 2024
Historique:
received:
23
01
2024
accepted:
03
06
2024
medline:
11
7
2024
pubmed:
11
7
2024
entrez:
11
7
2024
Statut:
aheadofprint
Résumé
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.
Identifiants
pubmed: 38989743
doi: 10.1097/CJI.0000000000000534
pii: 00002371-990000000-00113
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
M.T. received speakers’ and consultants’ fee from Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre, Amgen, Merck, Sanofi. M.T. received institutional research grants from Astra-Zeneca, Boehringer Ingelheim. The other authors have declared that there are no financial conflicts of interest with regard to this work.
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