Intersecting Blood Cytokines With Cholesterol Parameters to Profile Patients With Advanced Solid Tumors Receiving Immune Checkpoint Inhibitors

Overview

Journal J Immunother

Specialty Allergy & Immunology

Date 2024 Jul 11

PMID 38989743

Authors

Giulia Mazzaschi

Fabiana Perrone

Giuseppe Maglietta

Elda Favari

Michela Verze

Monica Pluchino

Roberta Minari

Federica Pecci

Letizia Gnetti

Nicoletta Campanini

Enrico Maria Silini

Massimo De Filippo

Michele Maffezzoli

Giulia Claire Giudice

Irene Testi

Marcello Tiseo

Federico Quaini

Sebastiano Buti

Affiliations

Soon will be listed here.

Abstract

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-6 low and IL-10 low cases ( P <0.05), whereas ABCA1-mediated CE was increased in IL-10 high patients ( P =0.018). Uni- and multivariable analysis revealed meaningfully longer OS and PFS in IL-6 low (HR 2.13 and 2.97, respectively) and IL-10 low (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.

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