[HTML][HTML] PD-1/PD-L1 interaction up-regulates MDR1/P-gp expression in breast cancer cells via PI3K/AKT and MAPK/ERK pathways

S Liu, S Chen, W Yuan, H Wang, K Chen, D Li, D Li - Oncotarget, 2017 - ncbi.nlm.nih.gov
S Liu, S Chen, W Yuan, H Wang, K Chen, D Li, D Li
Oncotarget, 2017ncbi.nlm.nih.gov
Programmed cell death ligand 1 (PD-L1) is an immunosuppressive molecule expressed on
tumor cells. By interacting with programmed cell death-1 (PD-1) on T cells, it inhibits immune
responses. Because PD-L1 expression on cancer cells increases their chemoresistance, we
investigated the correlation between PD-L1 and multidrug resistance 1/P-glycoprotein
(MDR1/P-gp) expression in breast cancer cells. Analysis of breast cancer tissues using
tissue microarrays revealed a significant correlation between PD-L1 and MDR1/P-gp protein …
Abstract
Programmed cell death ligand 1 (PD-L1) is an immunosuppressive molecule expressed on tumor cells. By interacting with programmed cell death-1 (PD-1) on T cells, it inhibits immune responses. Because PD-L1 expression on cancer cells increases their chemoresistance, we investigated the correlation between PD-L1 and multidrug resistance 1/P-glycoprotein (MDR1/P-gp) expression in breast cancer cells. Analysis of breast cancer tissues using tissue microarrays revealed a significant correlation between PD-L1 and MDR1/P-gp protein levels. Increased expression of PD-L1 was associated with lymph node metastasis and histological tumor grade. In addition, interaction of PD-L1 with PD-1 induced phosphorylation of AKT and ERK, resulting in the activation of PI3K/AKT and MAPK/ERK pathways and increased MDR1/P-gp expression in breast cancer cells. The PD-1/PD-L1 interaction also increased survival of breast cancer cells incubated with doxorubicin. These findings suggest that the PD-1/PD-L1 inhibition may increase chemotherapy efficacy by inhibiting the MDR1/P-gp expression in breast cancer cells.
ncbi.nlm.nih.gov