Serum cytokines and neutrophil-to-lymphocyte ratio as predictive biomarkers of benefit from PD-1 inhibitors in gastric cancer

Immunotherapy is significantly revolutionizing cancer treatment and demonstrating promising efficacy in gastric cancer (GC) patients. However, only a subset of patients could derive benefits from targeted monoclonal antibody therapy against programmed death receptor 1 (PD-1). This study aims to identify suitable serum cytokines and blood cell ratios as predictive biomarkers to aid in the selection of GC patients likely to benefit from PD-1 inhibitors. This retrospective study included 41 GC patients who received PD-1 inhibitors combined with chemotherapy, 36 GC patients treated solely with chemotherapy, and 33 healthy controls. The study assessed the levels of seven cytokines: interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and various inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), total lymphocyte count (TLC), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). Measurements were obtained using the inpatient system. Univariate and multivariate Cox regression analyses were performed to evaluate the predictive significance of these hematologic parameters for clinical outcomes. Levels of IL-6, IL-10, TNF-α, NLR, and PLR were significantly elevated in GC patients compared to healthy controls, while TLC and LMR were higher in the control group. Among the 41 patients receiving PD-1 inhibitors and chemotherapy, baseline IL-2 was associated with OS and PFS. Additionally, IL-6 and IL-17A correlated with OS, while NLR was linked to PFS (all P