Circulating cytokines as potential dynamic biomarkers of PD-1 blockade response and prognosis in non-small cell lung cancer

Programmed death 1 (PD-1) inhibitors have transformed the treatment of advanced non-small cell lung cancer (NSCLC), but durable responses remain limited to a subset of patients. Conventional biomarkers, including PD-L1 expression and tumor mutational burden, are constrained by tissue accessibility, intratumoral heterogeneity, and limited capacity for dynamic monitoring. Circulating cytokines offer a minimally invasive alternative because they reflect systemic inflammation, antitumor immunity, and treatment-related immune activation. Evidence indicates that serum levels and on-treatment changes in TNF-α, IFN-γ, IL-6, IL-8, IL-17A, IL-1β, IL-2, IL-5, and IL-10 are associated with response, survival, and immune-related adverse events during PD-1 blockade. In general, declines in IL-6, IL-8, IL-17A, and IL-10, together with transient increases in IFN-γ and TNF-α, may indicate favorable immune reinvigoration, although findings remain inconsistent across studies. This review summarizes the biological functions, mechanistic roles, and clinical relevance of circulating cytokines as dynamic biomarkers, evaluates their potential values and current limitations in predicting the efficacy of PD-1 inhibitor therapy in NSCLC.