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.
|Journal||Cancer Immunology, Immunotherapy|
|Publication status||E-pub ahead of print - 24 Feb 2023|
Bibliographical noteFunding Information:
Alessio Cortellini received speaker fees and grant consultancies by AstraZeneca, MSD, BMS, Roche, Novartis and EISAI. Luca Cantini is granted by ESMO with an ESMO Translational Research Fellowship. Any views, opinions, findings, conclusions or recommendations expressed in this material are those solely of the author(s) and do not necessarily reflect those of ESMO. Melissa Bersanelli received research funding (Institutional) from Roche S.p.A., Pfizer, Seqirus UK, Novartis, Bristol Myers Squibb (BMS), AstraZeneca, Sanofi Genzyme; honoraria as a speaker at scientific events and for advisory role (personal fees) from BMS, MSD, Novartis, AstraZeneca, Pierre Fabre, Pfizer, IPSEN; personal fees for copyright transfer from SciClone Pharmaceuticals, IPSEN, Pierre Fabre, MSD, Sanofi Genzyme. Marcello Tiseo: He received honoraria for advisory boards and/or speakers’ fee for AstraZeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre, Amgen and Merck, Sanofi. Research Grants from AstraZeneca and Boehringer Ingelheim. Sebastiano Buti: He received honoraria as a speaker at scientific events and advisory role by BMS, Pfizer, MSD, Ipsen, AstraZeneca and Novartis; he also received research funding from Novartis. The remaining authors have no conflicts of interest to declare.
Dr Alessio Cortellini acknowledges the support provided by the NIHR Imperial BRC.
© 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.