Circulating immune and biochemical markers predict tumor response to immunotherapy in advanced melanoma and lung cancer

Introduction: Peripheral immune biomarkers provide a minimally invasive approach to monitor systemic responses to cancer immunotherapy, yet their predictive value in real-world longitudinal settings remains incompletely defined. Methods: We conducted a prospective longitudinal study in patients with advanced melanoma and non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors. Thirteen circulating immune, inflammatory, and nutritional biomarkers were analyzed across treatment cycles, and their association with radiological response over time was assessed using Bayesian ordinal mixed-effects models. Results: Nine biomarkers showed significant longitudinal associations with clinical outcomes. CD4+ T cells emerged as the strongest predictor of favorable response, followed by CD3+ and CD45+ T cells, natural killer cells, albumin, and total protein, whereas elevated neutrophils, lactate dehydrogenase, and the neutrophil-to-lymphocyte ratio were associated with poor outcomes. No significant effects were observed for CD8+ T cells, B cells, total lymphocytes, or the CD4/CD8 ratio. Discussion: These findings identify circulating CD4+ T cells as the most informative peripheral biomarker associated with longitudinal response to immune checkpoint inhibitors and support the clinical utility of peripheral immune profiling as a dynamic, minimally invasive strategy for monitoring treatment efficacy in routine oncology practice.