NLR stability predicts response to immune checkpoint inhibitors in advanced hepatocellular carcinoma

• Published in: Scientific reports Vol. 14; no. 1; pp. 19583 - 12
• Main Authors: Du, Jiajia, Huang, Zhiyong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.08.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250; 631/250/251; 631/250/256; Adult; Aged; aHCC; Biomarkers; Biomarkers, Tumor; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - pathology; Female; Hepatocellular carcinoma; Humanities and Social Sciences; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - therapeutic use; Immune response; Immunotherapy; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - immunology; Liver Neoplasms - pathology; Male; Medical prognosis; Middle Aged; multidisciplinary; Neutrophils - immunology; NLR stability; PD-L1; PD-L1 protein; Prognosis; Retrospective Studies; Science; Science (multidisciplinary); Survival analysis; Training; PD-L1; aHCC; OS; NLR stability; Immunotherapy
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-68048-9

A high baseline NLR is associated with a poor prognosis of immunotherapy in patients with advanced HCC. As anti-tumour immune activation takes time, early dynamic changes in NLR may serve as a biomarker for predicting immunotherapy response. We conducted a retrospective study in which we enrolled 209 patients with aHCC who received ICIs (training cohort: N = 121, validation cohort: N = 88). In the training cohort, we categorized the patients based on the early changes in their NLR. Specifically, we defined patients as NLR Stable-Responder, NLR Responder and NLR Non-Responder. We compared the outcomes of these three patient groups using survival analysis. Additionally, we shortened the observation period to 6 weeks and validated the findings in the validation cohort. In the training cohort, early dynamic changes in NLR (HR 0.14, 95%CI 0.03–0.65, p  = 0.012, HR 0.19, 95%CI 0.07–0.54, p  = 0.002; HR 0.21, 95%CI 0.10–0.42, p  < 0.001, HR 0.40, 95%CI 0.23–0.69, p  = 0.001), PD-L1 < 1% (HR 5.36, 95%CI 1.12–25.66, p  = 0.036; HR 2.98, 95%CI 1.51–5.91, p  = 0.002) and MVI (HR 3.52, 95%CI 1.28–9.69, p  = 0.015; HR 1.99, 95%CI 1.14–3.47, p  = 0.015) were identified as independent predictors of OS and PFS. In the validation cohort, when the observation period was reduced to 6 weeks, early NLR changes still have predictive value. Early dynamic changes in NLR may be an easily defined, cost-effective, non-invasive biomarker to predict aHCC response to ICIs.