• Yongjia Yan, Zexuan Shen, Yanghee Woo, Daohan Wang, Xin Liu, Wenxin Zhang, Zhaoxiong Zhang, Peiyao Wang, and Weihua Fu.
• Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
• J. Am. Coll. Surg. 2024 Dec 19.

BackgroundImmunotherapy has achieved effective antitumor activity in advanced GC patients. However, the rate of response to ICI therapy is disappointing, T cell exhaustion may contribute to this phenomenon. EBI3 is an emerging immunosuppressive factor, and the association between EBI3 and T cell exhaustion is not clear. In this study, we aimed to explore the expression of EBI3 in GC, and reveal the function of EBI3 in T cell exhaustion.Study DesignThe gene expression data and clinical data of GC patients were downloaded from the TCGA database to measure the expression of EBI3 in GC and explore the association between EBI3 and clinicopathological features. Then tumor specimens were collected and IHC was used to demonstrate the expression of EBI3 in GC tissues. Finally, we constructed a mouse model of orthotopic GC to examine the function of EBI3 in T cell exhaustion.ResultsThe data from the TCGA database showed that EBI3 is highly expressed in GC and the expression of EBI3 is associated with pTNM stage. We analyzed the expression of EBI3 in GC tissues, the results showed expression of EBI3 is associated with age, T stage, N stage, pTNM stage, and degree of differentiation. After constructing the mouse model of orthotopic GC, we found EBI3 can lead to an increase in proportion of CD8+PD-1+T cells and CD8+LAG3+T cells, meanwhile, the secretion of IL-2 was significantly decreased.ConclusionOur study indicated that EBI3 is an important cytokine in the development of GC, and EBI3 may promote the development of GC by inducing T cell exhaustion in the tumor microenvironment.Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.

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