Soluble LAG3 acts as a potential prognostic marker of gastric cancer and its positive correlation with CD8+T cell frequency and secretion of IL-12 and INF-γ in peripheral blood.

Abstract

Gastric cancer (GC) is the second most common lethal cancer worldwide and lymphocyte-activation gene 3 (LAG3) as a therapeutic target for cancers has been investigated. Herein, our study is to clarify the value of peripheral blood (PB) soluble LAG-3 (sLAG3) in GC. Peripheral serum samples of GC patients and healthy people were collected for the measurement of serum levels of sLAG3, carcinoembryonic antigen (CEA), IL-12 and IFN-γ. Additionally, ROC and Kaplan-Meier curves were adopted to identify the diagnostic and prognostic values of sLAG-3 in patients with GC. Then, GC-bearing mice were treated with recombinant sLAG3. The tumor volume was measured, and CD8+T cell frequency was detected in PB and tumor-ininfiltrating area. Additionally, the expression of IL-12 and IFN-γ in T cells was assayed and the overall survival of mice was analyzed. sLAG3 in PB was poorly expressed and its expression was positively correlated with IL-12 and IFN-γ expression in GC patients. sLAG3 was proved to have a higher diagnostic value than CEA in GC. Moreover, high sLAG-3 expression is found in relation to a better prognosis in GC. The in vivo experiments indicated that sLAG-3 might inhibit the tumor growth, and promote the secretion of CD8+T cells, IL-12 and IFN-γ. Furthermore, sLAG-3 was able to prolong overall survival and increase survival rate of GC-bearing mice. Based on these findings, we conclude that sLAG3 positively regulates CD8+T cells, IL-12 and IFN-γ, and function as a prognostic marker for GC, which might be a potential target in the treatment of GC.