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
2025
Alina Miruna Grecea-Balaj | Olga Soritau | Ioana Brie | Maria Perde-Schrepler | Piroska Virag | Eva Fischer-Fodor | Nicolae Todor | Mihai Cenariu | Ioana Nedelea | Tudor Eliade Ciuleanu
This prospective single-center study examined associations between serum cytokines&mdash:TNF-&alpha:, IL-2, and IL-10&mdash: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-&alpha: increases, while NSCLC patients displayed heterogeneous cytokine dynamics. In NSCLC, elevated IL-10 at 3 months correlated with shorter survival (&rho: = &minus:0.51, 95% CI &minus:0.78 to &minus:0.12, p = 0.022) and poorer response (&rho: = &minus:0.65, 95% CI &minus:0.86 to &minus:0.23, p = 0.002). TNF-&alpha: showed a borderline association with response (&rho: = &minus:0.44, 95% CI &minus:0.74 to 0.01, p = 0.050). In melanoma, 3-month TNF-&alpha: was inversely associated with survival (&rho: = &minus:0.82, 95% CI &minus:0.97 to &minus:0.15, p = 0.023) and response (&rho: = &minus:0.90, 95% CI &minus:0.99 to &minus:0.39, p = 0.006). Strong inter-cytokine correlations were observed (NSCLC: TNF-&alpha: vs. IL-10, &rho: = 0.60, 95% CI 0.19&ndash:0.82: melanoma: &rho: = 0.93, 95% CI 0.44&ndash: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.
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