可溶性 LAG3 可作为胃癌的潜在预后标志物，其与外周血 CD8+T 细胞频率以及 IL-12 和 INF-γ 的分泌呈正相关。

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.

出版信息

Cancer Biomark. 2018;23(3):341-351. doi: 10.3233/CBM-181278.

Abstract

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

目的

胃癌（GC）是全球第二大常见致命癌症，淋巴细胞激活基因 3（LAG3）已被作为癌症的治疗靶点进行研究。在此，我们的研究旨在阐明外周血（PB）可溶性 LAG-3（sLAG3）在 GC 中的价值。

方法

收集 GC 患者和健康人的外周血清样本，用于测量血清 sLAG3、癌胚抗原（CEA）、IL-12 和 IFN-γ 的水平。此外，采用 ROC 和 Kaplan-Meier 曲线来确定 sLAG3 在 GC 患者中的诊断和预后价值。然后，用重组 sLAG3 处理荷瘤小鼠。测量肿瘤体积，并检测 PB 和肿瘤浸润区 CD8+T 细胞的频率。此外，检测 T 细胞中 IL-12 和 IFN-γ 的表达，并分析小鼠的总生存率。

结果

PB 中的 sLAG3 表达水平较低，其表达与 GC 患者的 IL-12 和 IFN-γ 表达呈正相关。sLAG3 在 GC 中的诊断价值高于 CEA。此外，高 sLAG-3 表达与 GC 患者的较好预后相关。体内实验表明，sLAG3 可能抑制肿瘤生长，并促进 CD8+T 细胞、IL-12 和 IFN-γ 的分泌。此外，sLAG3 能够延长 GC 荷瘤小鼠的总生存期并提高其存活率。