ORIGINAL RESEARCH article
Front. Immunol.
Sec. T Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1498706
This article is part of the Research TopicDrug Development for Pancreatic Cancer: Novel Targets, Drug Candidates and MechanismsView all 4 articles
Co-expression of IL-15/IL-15Ra complex enhances NKG2D-CAR T cell-mediated anti-pancreatic cancer immunity by activating the JAK/STAT5 signaling pathway
Provisionally accepted
Wenzheng Jiang*
Yiran ChenChenxu JinDandan GuoXinhui HuiYuzhou JiYunhe HuangMin Xue
Yaoxin GaoYaojun RenHaizhen LinYing Zhou- East China Normal University, Shanghai, China
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The application of CAR T therapy has significantly improved the efficacy of hematological tumors. However, there are still some challenges in the treatment of solid tumors, mainly because the complex immune microenvironment affects the proliferation of T cells, making T cells unable to function well. IL-15 has been reported to be a cytokine that can activate T cells and promote the proliferation and survival of T cells, especially CD8 + T cells. The complex formed by the high-affinity binding of IL-15 and IL-15Rα can bind to IL-2/IL-15Rb/g heterodimer on the surface of T cells, thereby activating downstream signaling pathways in T cells. In this study, we explored the activity of NKG2D-CAR T expressing IL-15/IL-15Rα complex (IL15C) on pancreatic cancer. The results of in vitro experiments showed that CAR T cells expressing IL15C had a stronger killing effect on tumor cells and showed a dose-dependent effect. In addition, the proliferation and anti-apoptosis levels of CAR T cells were enhanced after the co-expression of IL15C. IL15C regulates the function of T cells by activating the JAK/STAT5 signaling pathway of T cells. In vivo experiments showed that IL15C-NKG2D-CAR T cells could better inhibit tumor growth than the control group. This study provides a new idea for improving the efficacy of CAR T cells in the treatment of pancreatic cancer.
Keywords: NKG2D, CAR T, IL-15, Pancreatic carcinoma, JAK/STAT5
Received: 19 Sep 2024; Accepted: 04 Jun 2025.
Copyright: © 2025 Jiang, Chen, Jin, Guo, Hui, Ji, Huang, Xue, Gao, Ren, Lin and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wenzheng Jiang, East China Normal University, Shanghai, China
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