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

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.