Gastric cancer mesenchymal stem cells upregulate PD-1 expression on the CD8+ T cells by regulating the PI3K/AKT pathway

Abstract

Gastric cancer mesenchymal stem cells (GC-MSCs) are a crucial component of the gastric cancer microenvironment, exerting a pivotal influence on the formation of a suppressive immune microenvironment and the progression of gastric cancer. In this study, we utilized GC-MSCs to co-culture peripheral blood mononuclear cells (PBMCs) obtained from both gastric cancer patients and healthy individuals in a proportionate manner by direct cell-to-cell contact. Our findings reveal that co-culture of GC-MSCs with PBMCs led to a notable reduction in CD8⁺ T cells percentages and an increase in surface PD-1 expression levels on CD8⁺ T cells. However, flow cytometry analysis demonstrated no significant changes following pretreatment with GC-MSC-conditioned medium (GC-MSC-CM). Moreover, western blotting analysis demonstrated a notable reduction in phosphorylated AKT levels in co-cultured PBMCs. Collectively, our results suggest that GC-MSCs impair the anti-tumor immune response of PBMCs by elevating the PD-1 levels of CD8⁺ T cells and impairing the killing of CD8⁺ T cells. These findings provide new evidence that GC-MSCs contribute to immunosuppression within the tumor microenvironment (TME).