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Although immunotherapy has demonstrated clinical efficacy in advanced gastric cancer (AGC), its therapeutic benefits are limited to a subset of patients. This study aimed to evaluate circulating cytokines as potential prognostic biomarkers to enhance the precision of clinical decision-making in PD-1 inhibitor-based immunotherapy for AGC. A total of 269 patients with advanced gastric cancer were enrolled according to predefined inclusion criteria. Among them, 117 patients received anti-PD-1 immunotherapy combined with chemotherapy (immunochemotherapy), while 152 received chemotherapy alone. Plasma levels of 12 cytokines were quantified using flow cytometry, and appropriate statistical analyses were performed. Compared with healthy controls, plasma concentrations of IL-6, IL-8, and IL-10 were significantly elevated in AGC patients. Furthermore, levels of these cytokines were markedly higher in the immunochemotherapy no response group compared to both the chemotherapy-alone group and response group. Multivariate analysis confirmed that IL-6, IL-8, and IL-10 were independent risk factors for poor treatment outcomes in patients receiving immunochemotherapy. Notably, the combined measurement of these three cytokines provided superior diagnostic accuracy compared to individual markers. The present study preliminarily demonstrates that IL-6, IL-8, and IL-10 cytokines may serve as potential predictive biomarkers for treatment outcomes in patients with AGC receiving anti-PD-1 immunochemotherapy. These easily accessible blood biomarkers are predictive and rapid and may play a key role in identifying individuals who may benefit from PD-1 blockade immunotherapy.