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24-02-2023 | NSCLC | Research

The role of blood cholesterol quality in patients with advanced cancer receiving immune checkpoint inhibitors

Authors: Fabiana Perrone, Elda Favari, Giuseppe Maglietta, Michela Verzè, Monica Pluchino, Roberta Minari, Roberto Sabato, Giulia Mazzaschi, Annalisa Ronca, Alessandra Rossi, Alessio Cortellini, Federica Pecci, Luca Cantini, Melissa Bersanelli, Federico Quaini, Marcello Tiseo, Sebastiano Buti

Published in: Cancer Immunology, Immunotherapy | Issue 7/2023

Abstract

Introduction

Immune checkpoint inhibitors (ICIs) became the standard of care for several solid tumors. A limited fraction of patients (pts) achieves a long-term benefit. Plasmatic and intracellular cholesterol levels have emerged as promising biomarkers. The aim of the present study was to determine whether cholesterol efflux capacity (CEC), mediated by serum transporters (ABCA1 and ABCG1) and passive diffusion (PD), impacts on clinical outcome of advanced non-small cell lung cancer (NSCLC) and metastatic renal cell carcinoma (mRCC) pts treated with ICIs.

Material and methods

We retrospectively enrolled advanced NSCLC and mRCC pts consecutively treated with ICIs between October 2013 and October 2018. CEC and cholesterol loading capacity (CLC) were assessed by well-established specific cell models. As primary endpoint, CEC, PD and CLC were correlated with overall survival (OS) while the effects of these parameters on progression-free survival (PFS) and clinical benefit (CB), defined as complete/partial response or stable disease, represented secondary endpoints.

Results

NSCLC accounted for 94.2% of 70 enrolled cases, and serum sample suitable for CEC and PD determination was available in 68. Blood cholesterol and serum ABCA1, ABCG1, PD and CLC were associated with outcomes (OS, PFS and CB) at univariate analysis. At the multivariate analysis, only PD confirmed its positive prognostic value in terms of OS, PFS and CB.

Conclusion

The favorable impact of cholesterol PD on clinical outcome might reflect its main conformation in mature HDL particles which potentially shape an inflamed context, ultimately promoting ICI efficacy. Further prospective studies are needed to support our findings and uncover targetable pathways.

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Title: The role of blood cholesterol quality in patients with advanced cancer receiving immune checkpoint inhibitors
Authors: Fabiana Perrone
Elda Favari
Giuseppe Maglietta
Michela Verzè
Monica Pluchino
Roberta Minari
Roberto Sabato
Giulia Mazzaschi
Annalisa Ronca
Alessandra Rossi
Alessio Cortellini
Federica Pecci
Luca Cantini
Melissa Bersanelli
Federico Quaini
Marcello Tiseo
Sebastiano Buti
Publication date: 24-02-2023
Publisher: Springer Berlin Heidelberg
Keywords: NSCLC
NSCLC
Checkpoint Inhibitors
Published in: Cancer Immunology, Immunotherapy / Issue 7/2023
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-023-03398-3

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Abstract

Introduction

Material and methods

Results

Conclusion

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