Peripheral blood T lymphocytes are downregulated by the PD-1/PD-L1 axis in advanced gastric cancer

Abstract

Introduction: Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) function as an immune checkpoint pathway that can be exploited by tumor cells to evade immuno-surveillance. The precise role of PD-1/PD-L1 inhibition of the immune response in GC is unknown. The study investigated PD-1 and PD-L1 expression on peripheral T-cells and its potential association with clinicopathological features in gastric cancer (GC) patients. Material and methods: PD-1/PD-L1 expression on CD4(+) and CD8(+) T-cells from peripheral blood of 40 patients primarily diagnosed with advanced GC was evaluated by multicolor flow cytometry. Results: The frequency of CD4(+)PD-1(+) and CD8(+)PD-1(+) cells in GC patients was higher than in the control group (p < 0.0001 and p < 0.01, respectively). Expression of PD-1 on CD8(+) cells in GC was higher than in the control group (p < 0.0001). The frequency of CD4(+)PD-L1(+) and CD8(+) PD-L1(+) cells was higher than in the control group (p < 0.0001). Expression of PD-L1 on CD4(+) and CD8(+) cells in GC was higher than in the control group (p < 0.0001). A higher frequency of CD4(+)PD-1(+) cells was found in diffuse-type compared to intestinal tumors (p < 0.029). A higher frequency of CD8(+)PD-1(+) cells was found in patients with poorly differentiated compared to well/moderately differentiated tumors (p < 0.019). Conclusions: Downregulation of peripheral blood CD4(+) and CD8(+) lymphocytes can be associated with PD-1/PD-L1 expression. This can lead to attenuation of the general immune response in GC.