Effect of IL-6, IL-8, and IL-17A on Predicting Treatment Outcomes in PD-1 Blockade Immunochemotherapy in Advanced Gastric Cancer

Introduction Advanced gastric cancer (AGC) treatment outcomes are improved with PD-1 blockade immunochemotherapy, but predicting responders remains challenging. Cytokines, key immune response regulators, may predict treatment outcomes. Aims: This study investigates the potential of cytokines as predictive biomarkers in AGC patients. Material and methods In this retrospective analysis, 241 patients with AGC were included, with 136 patients receiving an immunochemotherapy regimen that included PD-1 blockade, while 105 patients constituted the control group receiving chemotherapy alone. Serum levels of various cytokines (IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-1β, IL-17A, IFN-α2, IFN-γ, TNF-α and IL-12p70) were measured using a Luminex after the initiation of treatment. Results Patients undergoing PD-1 blockade immunochemotherapy demonstrated a significant elevation in the levels of IL-6, IL-8, and IL-17A, especially within the group that exhibited a therapeutic response, when compared to the control group. Notably, among those who responded to the immunochemotherapy, there was a marked reduction in the concentrations of IL-6, IL-8, and IL-17A over the course of the treatment. In contrast, such reductions were not observed in the non-response group. Among the assessed cytokines, the combined evaluation of IL-6, IL-8, and IL-17A, in conjunction with CA-125, demonstrated the highest predictive accuracy for assessing the efficacy of immunochemotherapy in AGC patients. Conclusions Our study identifies IL-6, IL-8, and IL-17A cytokines as predictive biomarkers for treatment outcomes in AGC patients receiving immunochemotherapy. Combining these cytokines with CA-125 significantly enhances predictive accuracy, enabling tailored treatment strategies to improve patient outcomes.