Immune Phenotyping Using Neutrophil-to-Lymphocyte Ratio and Tumor-Infiltrating Lymphocytes Predicts Recurrence in...

Background and Objectives: Tumor-infiltrating lymphocytes (TIL) and the neutrophil-to-lymphocyte ratio (NLR) are each associated with prognosis in melanoma, yet their combined prognostic value remains insufficiently defined. We aimed to assess whether integrating NLR and TILs into a combined immune phenotype improves prediction of recurrence-free survival (RFS) in patients with resected cutaneous melanoma. Materials and Methods: A total of 203 patients were included. Receiver operating characteristic analysis identified an NLR cut-off of 2.75 for RFS, defining low (<2.75) and high (≥2.75) groups. TIL status was dichotomized as present or absent. According to the combined NLR-TIL profile, patients were initially categorized into three immune phenotypes: favorable (low NLR and TIL-positive), intermediate (low NLR and TIL-negative or high NLR and TIL-positive), and unfavorable (high NLR and TIL-negative). For the dichotomized analysis, the intermediate and unfavorable phenotypes were combined and compared with the favorable phenotype. Associations of clinicopathological factors with RFS were evaluated using Kaplan-Meier curves and Cox regression models. Results: The median follow-up was 56 months. In the univariate analysis, stage III disease, greater Breslow thickness, increased mitotic rate, and absence of adjuvant therapy were associated with worse RFS. In addition, patients with an unfavorable immune phenotype had a markedly increased risk of recurrence compared with those in the favorable group (HR 2.86, 95% CI 1.43-5.71; p = 0.004). In multivariate Cox regression analysis, both the unfavorable immune phenotype and stage III disease independently predicted RFS (HR 2.25, 95% CI 1.11-4.54; p = 0.024 and HR 2.13, 95% CI 1.03-4.43; p = 0.041, respectively). Conclusions: Combined assessment of systemic inflammation and tumor-local immune response using NLR and TILs may provide meaningful prognostic stratification in resected cutaneous melanoma.