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SJTU Research Team Proposed New Thoughts on Gastric Cancer Immunotherapy

March 23, 2020      Author: Ma Bin

On March 10, 2020, Gao Weiqiang and Ma Bin's team from School of Biomedical Engineering, SJTU published their research paper "Blockade of β-catenin-induced CCL28 suppresses gastric cancer progression via inhibition of Treg cell infiltration" in Cancer Research, an internationally renowned journal under American Association for Cancer Research (AACR).

The first author of this research is doctoral student Ji Lu, and the co-corresponding authors are Professor Gao Weiqiang and Professor Ma Bin. The research was supported by National Key R&D Plan of MOST, National Natural Science Foundation of China, Shanghai Young Oriental Scholar, and K. C. Wong Education Foundation.

Abstract:

Dysregulation of Wnt/β-catenin signaling is frequently observed in human gastric cancer. Elucidation of the tumor immune microenvironment is essential for understanding tumorigenesis and for the development of immunotherapeutic strategies. However, it remains unclear how β-catenin signaling regulates the tumor immune microenvironment in the stomach. Here we identify CCL28 as a direct transcriptional target gene of β-catenin/T cell factor (TCF). Protein levels of β-catenin and CCL28 positively correlated in human gastric adenocarcinoma. Activation of CCL28 by β-catenin recruited Regulatory T (Treg) cells in a transwell migration assay. In a clinically relevant mouse gastric cancer model established by Helicobacter (H.) felis infection and MNU treatment, inhibition of β-catenin/TCF activity by a pharmacological inhibitor iCRT14 suppressed CCL28 expression and Treg cell infiltration in the stomach. Moreover, an anti-CCL28 antibody attenuated Treg cell infiltration and tumor progression in H. felis/MNU mouse models. Diphtheria toxin (DT)-induced Treg cell ablation restrained gastric cancer progression in H. felis/MNU-treated DEREG (Foxp3-DTR) mice, clarifying the tumor-promoting role of Treg cells. Thus, the β-catenin-CCL28-Treg cell axis may serve as an important mechanism for immunosuppression of the stomach tumor microenvironment. Our findings reveal an immunoregulatory role of β-catenin signaling in stomach tumors and highlight the therapeutic potential of CCL28 blockade for the treatment of gastric cancer.

 

Link: https://cancerres.aacrjournals.org/content/early/2020/03/10/0008-5472.CAN-19-3074



Translated by Li Wenqi     Reviewed by Wang Bingyu