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

<b>Aim:</b> 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. <b>Methods:</b> We retrospectively collected total cholesterol (TC), triglycerides (TGs), low-density lipoproteins (LDL), high-density lipoproteins (HDL). <b>Results:</b> 407 patients were enrolled. In NLR &lt;4 subgroup, TGs &lt;150 mg/dl led to longer PFS (<i>p</i> = 0.01) and OS (<i>p</i> = 0.02) compared with TGs ≥150 mg/dl; LDL &lt;100 mg/dl led to longer PFS (<i>p</i> = 0.004) and OS (<i>p</i> = 0.007) compared with LDL ≥100 mg/dl. In NLR ≥4 subgroup, TC &gt;200 mg/dl led to longer PFS (<i>p</i> = 0.008) and OS (<i>p</i> = 0.004) compared with TC &lt;200 mg/dl. <b>Conclusion:</b> We showed a distinct prognostic impact of lipid profile according to NLR. 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. 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. 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 &lt;4 under immunotherapy treatment. High LDL and high triglycerides negatively impact on clinical outcomes in patients with NLR &lt;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. 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.