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.