Differential impact of lipid profile according to neutrophil-to-lymphocyte ratio status in patients with advanced cancer treated with immunotherapy

Abstract

Aim: To investigate the different impact of each component of lipid profile in advanced cancer patients treated with immune checkpoints inhibitors (ICIs) according to neutrophil-to-lymphocyte ratio (NLR) value. Methods: We retrospectively collected total cholesterol (TC), triglycerides (TGs), low-density lipoproteins (LDL), high-density lipoproteins (HDL). Results: 407 patients were enrolled. In NLR <4 subgroup, TGs <150 mg/dl led to longer PFS (p = 0.01) and OS (p = 0.02) compared with TGs ≥150 mg/dl; LDL <100 mg/dl led to longer PFS (p = 0.004) and OS (p = 0.007) compared with LDL ≥100 mg/dl. In NLR ≥4 subgroup, TC >200 mg/dl led to longer PFS (p = 0.008) and OS (p = 0.004) compared with TC <200 mg/dl. Conclusion: We showed a distinct prognostic impact of lipid profile according to NLR.

Article highlights

Background

• Preclinical findings suggest a link between lipid metabolism, systemic inflammation and immune cells activity. In this study, the interaction between lipid profile and inflammatory status in cancer patients have been investigated.

Patients & methods

• A total of 407 patients with advanced solid tumors treated with ICIs, alone or in combination with TKIs or chemotherapy, were enrolled in the study. Clinical outcomes were investigated according to lipid profile components, in the whole cohort and in NLR-based subgroups.

Survival analyses

• The negative prognostic value of high NLR have been confirmed in patients with advanced cancer treated with immune checkpoints inhibitors.

• Components of lipid profile (total cholesterol, triglycerides, HDL, LDL) have a different prognostic impact according to NLR subgroups.

• High total cholesterol and preserved HDL positively impact on clinical outcomes in patients with NLR ≥4 under immunotherapy treatment.

• No prognostic impact on clinical outcomes was observed according to total cholesterol and HDL in patients with NLR <4 under immunotherapy treatment.

• High LDL and high triglycerides negatively impact on clinical outcomes in patients with NLR <4 under immunotherapy treatment.

• Conversely, no prognostic impact on clinical outcomes was observed according to LDL and triglycerides in patients with NLR ≥4 under immunotherapy treatment.

Conclusions

• Each component of circulating lipid profile detains distinct prognostic impact according to NLR subgroup.

• Our results supported the evidence about the close interconnecting between lipid profile and immune-inflammatory system in patients with advanced solid tumors receiving immunotherapy.

Keywords: :

• cholesterol
• immunotherapy
• lipid metabolism
• neutrophil-to-lymphocyte ratio
• systemic inflammation

Supplemental material

Supplemental data for this article can be accessed at https://doi.org/10.1080/1750743X.2024.2377953

Author contributions

Conception or design of the study: F Perrone, F Pecci, L Cantini, S Buti; data acquisition: F Perrone, M Maffezzoli, GC Giudice, V Cognigni, G Mazzaschi, L Santamaria, F Paoloni; data analysis: Pecci F, L Cantini; data interpretation: F Perrone, Pecci F, M Maffezzoli, GC Giudice, V Cognigni, G Mazzaschi, S Buti. All authors contributed to and approved the manuscript.

Financial disclosure

Luca Cantini and Kamal S Saini are employees of Fortrea Inc. Kamal S Saini reports consulting fees from the European Commission, and stock and/or other ownership interests in Fortrea Inc. and Quantum Health Analytics (UK) Ltd, outside the submitted work.Marcello Tiseo received speakers' and consultants' fees from AstraZeneca, Pfizer, Eli Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre, Amgen, Merck, and Sanofi, as well as institutional research grants from AstraZeneca and Boehringer Ingelheim. Rossana Berardi reported serving as a consultant/adviso- ry board member for AstraZeneca, Boehringer Ingelheim, Novartis, Merck, Otsuka, Eli Lilly, and Roche. Sebastiano Buti received honoraria as speaker at scientif- ic events and advisory role by Bristol-Myers Squibb (BMS), Pfizer, MSD, Ipsen, Roche, AstraZeneca, and Novartis. The other authors indicated no financial relationships. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

S Buti received honoraria as speaker at scientific events and advisory role by Bristol-Myers Squibb (BMS), Pfizer, MSD, Ipsen, Roche, AstraZeneca and Novartis. R Berardi reported serving as a consultant/advisory board member for AstraZeneca, Boehringer Ingelheim, Novartis, Merck, Otsuka, Eli Lilly and Roche.

M Tiseo received speakers' and consultants' fees from AstraZeneca, Pfizer, Eli Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre, Amgen, Merck and Sanofi, as well as institutional research grants from AstraZeneca and Boehringer Ingelheim. L Cantini and SS Kamal are employees of Fortrea Inc.

The other authors indicated no financial relationships. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The study was approved by each participating center, after previous approval by the coordinating center (‘Comitato Etico Regionale delle Marche - C.E.R.M.’, Reference Number 19/792).