TNF+ regulatory T cells regulate the stemness of gastric cancer cells through the IL13/STAT3 pathway

Rou Zhao; Guanjie Cao; Baogui Zhang; Li Wei; Xiaobei Zhang; Meng Jin; Baoyu He; Bin Zhang; Zhun He; Qingli Bie

doi:10.3389/fonc.2023.1162938

TNF+ regulatory T cells regulate the stemness of gastric cancer cells through the IL13/STAT3 pathway

Front Oncol. 2023 Jul 18:13:1162938. doi: 10.3389/fonc.2023.1162938. eCollection 2023.

Authors

Rou Zhao¹, Guanjie Cao², Baogui Zhang³, Li Wei⁴, Xiaobei Zhang⁵, Meng Jin⁶, Baoyu He¹, Bin Zhang¹, Zhun He⁷, Qingli Bie¹

Affiliations

¹ Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, China.
² Department of Radiology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, China.
³ Colorectal Ward, Department of Gastrointestinal Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, China.
⁴ Department of Pathology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, China.
⁵ Medical Research Center, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, China.
⁶ Hernia and Abdominal Wall Surgery, Affiliated Hospital of Jining Medical University, Jining, Shandong, China.
⁷ Department of Thoracic Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, China.

Abstract

Regulatory T cells (Tregs) are an important component of the tumor microenvironment; however, the interaction between Tregs and gastric cancer cells is not completely understood. Recent studies have shown that Tregs participate in cancer cell stemness maintenance. In this study, we performed single-cell RNA sequencing of gastric cancer and adjacent tissues and found that Tregs with high TNF expression were recruited to gastric cancer tissues and were significantly correlated with patient survival. TNF+ Tregs significantly contribute to tumor growth and progression. Our studies have further demonstrated that TNF+ Tregs promote the stemness of gastric cancer cells through the IL13/STAT3 pathway. Therefore, blocking the interaction between TNF+ Tregs and gastric cancer cells may be a new approach in the treatment of gastric cancer.

Keywords: IL-13; TNF; Tregs; cancer stem cell; gastric cancer.

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 82273447, 82273069, 82173371), Project tsqn.201909192 supported by Tai Shan Young Scholar Foundation of Shandong Province, Shandong Provincial Natural Science Foundation (No. ZR2020YQ59), China Postdoctoral Science Foundation funded project (No.2022M711320, 2022M711322), Project 202003031182, 202003031183, 202002051197 supported by the Project of Medicine Health and Technology Development Plan of Shandong Province, “Youth Innovation Science and Technology Support Plan” of Shandong Province’s colleges and universities (No.2021KJ017), Ph.D. Research Foundation of the Affiliated Hospital of Jining Medical University (No. 2022-BS-003), the Miaopu Research of the Affiliated Hospital of Jining Medical University (No. MP-ZD-2020-005). Research Fund for New Drug and Clinical Translation Workstation of Academician Lin He of Jining Medical University (JYHL2022FZD04).