Serum TNF -α, IL-10 and IL-2 Trajectories and Outcomes in NSCLC and Melanoma Under Anti-PD-1 Therapy: Longitudinal Real-World Evidence from a Single Center.

Abstract

This prospective single-center study examined associations between serum cytokines-TNF-α, IL-2, and IL-10-and outcomes in stage IV non-small cell lung cancer (NSCLC, n = 43) and melanoma (n = 15) patients treated with Nivolumab at the Oncology Institute in Cluj-Napoca, Romania. Cytokines were measured at baseline (NSCLC: n = 43; melanoma: n = 15), 3 months (NSCLC: n = 20; melanoma: n = 7), and 6 months (NSCLC: n = 10; melanoma: n = 5). Melanoma patients showed sustained IL-2 and TNF-α increases, while NSCLC patients displayed heterogeneous cytokine dynamics. In NSCLC, elevated IL-10 at 3 months correlated with shorter survival (ρ = -0.51, 95% CI -0.78 to -0.12, p = 0.022) and poorer response (ρ = -0.65, 95% CI -0.86 to -0.23, p = 0.002). TNF-α showed a borderline association with response (ρ = -0.44, 95% CI -0.74 to 0.01, p = 0.050). In melanoma, 3-month TNF-α was inversely associated with survival (ρ = -0.82, 95% CI -0.97 to -0.15, p = 0.023) and response (ρ = -0.90, 95% CI -0.99 to -0.39, p = 0.006). Strong inter-cytokine correlations were observed (NSCLC: TNF-α vs. IL-10, ρ = 0.60, 95% CI 0.19-0.82; melanoma: ρ = 0.93, 95% CI 0.44-0.99). Baseline cytokines had limited utility, particularly in melanoma due to the small sample size. The most informative finding was the association of elevated 3-month IL-10 with adverse outcomes in NSCLC. These results support the value of dynamic cytokine monitoring in immunotherapy and warrant validation in larger cohorts.