Prognostic role and clinical association of neutrophil/lymphocyte ratio with immune infiltrates in gastric cancer

Abstract Background: Neutrophil/lymphocyte ratio (NLR) is a vital index for systemic inflammation and prognostic indicator for gastric cancer (GC). More details between NLR and prognosis were still obscure. The objective of this study was to analyze the role of NLR in different prognostic models and subgroups, and explore the mediating effects of immune infiltrates between NLR and survival.Methods: A total of 924 patients underwent D2 radical gastrectomy were enrolled in this study. According to the level of NLR, patients were divided into two groups, the high and low NLR groups. Clinical parameters, indexes related to immune infiltrates, and survival were compared between the two groups. Prognostic models, interaction analysis and mediating effects analysis were performed to investigate the clinical association of NLR, immune infiltrates, and survival.Results: The infiltration of CD3+ and CD8+ T cells was significantly different in the two NLR groups. The level of NLR was an independent prognostic predictor of GC. The NLR-adjusted pTNM staging models had better predictive value for patient prognosis when compared with the traditional pTNM staging system. In addition, an interaction effect exists between NLR and MMR status on the prognosis of GC (P-interaction <0.01). High level of NLR correlated with a better prognosis in patients with dMMR, while associated with a worse prognosis in patients with pMMR. Lastly, the mediating effect analysis revealed that the infiltration level of CD3+ T cells was the mediating factor between NLR and survival (P < 0.001). Conclusions: The level of NLR is an independent prognostic predictor of GC. Adding an index representing the level of NLR can improve the prognostic prediction value of TNM staging system in GC patients. The effect of NLR on prognosis is partly mediated by CD3+ T cells infiltration.