Co-expression of PD1/PD-L1 on Tumor Cells Is Involved in the Regulation of Cell Proliferation.

[BACKGROUND/AIM] Immune checkpoint inhibitors have recently been applied as anticancer agents for various thoracic malignancies. However, the mechanisms underlying their efficacy remain insufficiently understood. We therefore conducted a study to investigate the role of programmed cell death protein 1 (PD1) molecules expressed on the surface of cancer cell lines.

[MATERIALS AND METHODS] We assessed PD1 expression on the surface of nine cell lines using flow cytometry. To explore the involvement of the PD1/programmed cell death ligand 1 (PD-L1) axis in cell proliferation, we inhibited PD1 function by adding nivolumab to PD1-positive tumor cell lines. We then analyzed changes in cell proliferation signaling pathways of a small-cell lung cancer cell line, SBC-3, and changes in PD-L1 expression and associated signaling pathways by adding cobalt chloride and interferon-γ, known to influence PD-L1 expression .

[RESULTS] Among the nine cell-lines, SBC-3 showed strong PD1 expression, whereas the other eight cell lines exhibited minimal or no expression. Significant increases in cell proliferation were observed following treatment of SBC-3 cells with nivolumab at concentrations of 4 and 40 μg/ml. Immunoblotting analysis revealed enhanced phosphorylation of AKT serine/threonine kinase 1 and extracellular-regulated kinase, along with a concentration-dependent decrease in COP9 signalosome subunit 5 (CSN5) expression. Although cobalt chloride treatment increased expression of hypoxia-inducible factor 1α, it did not affect PD-L1 expression. In contrast, treatment with interferon-γ resulted in marked inhibition of cell proliferation and a clear decrease in PD-L1 expression.

[CONCLUSION] Co-expression of PD1 and PD-L1 may play a role in regulating proliferation of tumor cells, particularly in cases with strong PD1 expression on tumor cells.