Regulation of PD‐L1 expression by aPKCλ in cutaneous angiosarcoma

Summary

The expression of immune checkpoint proteins such as programmed cell death protein 1, PD‐1 and its ligand, PD‐L1 have been shown to correlate with patient prognosis in many malignant cancers. The expression of PD‐L1 is controlled by c‐Myc, however, further upstream regulation of PD‐L1 expression is largely unknown. We have previously shown that atypical protein kinase C lambda/iota (aPKCλ) phosphorylates the Forkhead box protein O1 (FoxO1) transcription factor at Ser218 to suppress its DNA binding ability, thereby regulating c‐Myc expression and controlling physiologic and pathologic endothelial proliferation. The presence of phosphorylation of FoxO1 at Ser218 (pSer218) FoxO1 in cutaneous angiosarcoma (CAS) strongly correlates with poor patient prognosis. Here, we reported that patients with PD‐L1 positive cells in CAS lesions demonstrated significantly worse prognosis compared to those that were the PD‐L1 negative. Expression of PD‐L1 correlated that of aPKCλ or the presence of pSer218FoxO1. Moreover, suppression of aPKCλ expression or inhibition of its activity in human umbilical vein endothelial cells (HUVECs) or AS‐M, an established human angiosarcoma cell line, resulted in decreased PD‐L1 expression. Our results suggest that combined treatment with immune checkpoint inhibitors and aPKCλ inhibitors may be a novel treatment strategy for CAS patients.

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