Submit Manuscript  

Article Details


Disruption of Wnt/β-catenin Pathway Elevates the Sensitivity of Gastric Cancer Cells to PD-1 Antibody

Author(s):

Jian Li, Hui Zhang, Songhua Bei, Xiaohong Zhang, Huanqing Li, Li Ye* and Li Feng*   Pages 1 - 13 ( 13 )

Abstract:


Background: Gastric Cancer (GC) is the fifth most common malignancy tumor and the third cause of cancer-related death around the world. Immune checkpoint inhibitors (ICIs) such as programmed cell death-1 (PD-1) antibodies play an active role in tumor therapy. A recent study reveals that Wnt/β-catenin signaling pathway is negatively correlated with T-cell infiltration in tumor microenvironment (TME), thereby influencing the therapeutic efficacy of PD-1 antibody.

Objective: In this study, we aimed to uncover the relationship of Wnt/β-catenin pathway to CD8+ T cell activity as well as its effect on anti-PD-1 therapeutic efficacy in GC.

Methods and Results: We first collected clinical samples and went through an immunohistochemical analysis and found that a high β-catenin expression in GC tissues was often associated with a significant absence of CD8+ T-cell infiltration. In addition, our data further indicated that disruption of the Wnt/β-catenin pathway in GC cells inhibited their migratory and invasive ability. Meanwhile, enhanced sensitivity of GC cells to PD-1 blockade therapy was evident by decreased Jurkat cell apoptosis rate and increased GC cell apoptosis rate in a tumor and Jurkat cells co-culture system with the presence of Wnt/β-catenin pathway inhibition.

Conclusion: Collectively, these findings indicated Wnt/β-catenin pathway may play a significant role in modulating the activity of Jurkat cells and downregulation of Wnt/β-catenin may enhance the sensitivity of GC cells to PD-1 antibody in vitro. This result further indicated that β-catenin and PD-1 targeted inhibition might become a potential and effective therapy for GC patients.

Keywords:

Gastric cancer, β-catenin, T-cell infiltration, immune checkpoint blockade, immunotherapy, malignant tumor.

Affiliation:

Endoscopy center, Minhang Hospital, Fudan University, Shanghai 201199, Department of Biological Medicines & Shanghai Engineering Research Center of Immuno Therapeutics, School of Pharmacy, Fudan University, Shanghai 201203, Endoscopy center, Minhang Hospital, Fudan University, Shanghai 201199, Endoscopy center, Minhang Hospital, Fudan University, Shanghai 201199, Endoscopy center, Minhang Hospital, Fudan University, Shanghai 201199, Department of Biological Medicines & Shanghai Engineering Research Center of Immuno Therapeutics, School of Pharmacy, Fudan University, Shanghai 201203, Endoscopy center, Minhang Hospital, Fudan University, Shanghai 201199



Read Full-Text article