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

被引：11

作者：

Perrone, Fabiana ^{[1
]}

Favari, Elda ^{[2
]}

Maglietta, Giuseppe ^{[3
]}

Verze, Michela ^{[1
]}

Pluchino, Monica ^{[1
]}

Minari, Roberta ^{[1
]}

Sabato, Roberto ^{[1
]}

Mazzaschi, Giulia ^{[1
,4
]}

Ronca, Annalisa ^{[2
]}

Rossi, Alessandra ^{[2
]}

Cortellini, Alessio ^{[5
]}

Pecci, Federica ^{[6
]}

Cantini, Luca ^{[6
,7
]}

Bersanelli, Melissa ^{[1
]}

Quaini, Federico ^{[4
]}

Tiseo, Marcello ^{[1
,4
]}

Buti, Sebastiano ^{[1
,4
]}

机构：

[1] Univ Hosp Parma, Med Oncol Unit, Parma, Italy

[2] Univ Parma, Food & Drug Dept, Parma, Italy

[3] Univ Hosp Parma, Clin & Epidemiol Res Unit, Parma, Italy

[4] Univ Parma, Dept Med & Surg, Parma, Italy

[5] Imperial Coll London, Hammersmith Hosp, Dept Surg & Canc, Div Canc, London, England

[6] Univ Politecn Marche, Clin Oncol, AOU Osped Riuniti, Ancona, Italy

[7] Erasmus MC Canc Inst, Dept Pulm Med, Rotterdam, Netherlands

来源：

CANCER IMMUNOLOGY IMMUNOTHERAPY | 2023年 / 72卷 / 07期

关键词：

Cholesterol efflux capacity; ABCA1; ABCG1; Passive diffusion; Cholesterol loading capacity; Immunotherapy; EFFLUX CAPACITY; HDL; TRANSPORTERS; TRAFFICKING; METABOLISM;

D O I：

10.1007/s00262-023-03398-3

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

IntroductionImmune 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 methodsWe 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.ResultsNSCLC 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.ConclusionThe 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.

引用

页码：2127 / 2135

页数：9

共 27 条

[1] The correlation of ATP-binding cassette 1 mRNA levels with cholesterol efflux from various cell lines [J].