Open AccessRegulation of programmed cell death ligand 1 expression by atypical protein kinase C lambda/iota in cutaneous angiosarcoma
Author(s) -
Kawamura Ai,
Kawamura Takuji,
Riddell Meghan,
Hikita Takao,
Yanagi Teruki,
Umemura Hiroshi,
Nakayama Masanori
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13981
Subject(s) - cancer research , immune checkpoint , pd l1 , angiosarcoma , foxo1 , phosphorylation , biology , immunohistochemistry , programmed cell death , transcription factor , immune system , kinase , immunotherapy , apoptosis , immunology , microbiology and biotechnology , medicine , pathology , biochemistry , protein kinase b , gene
The expression of immune checkpoint proteins such as programmed cell death protein 1 ( PD ‐1) and its ligand ( PD ‐L1) has 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 ( aPKC λ) 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 + cells in CAS lesions showed significantly worse prognosis compared to those that were PD ‐L1 − . Expression of PD ‐L1 correlated with that of aPKC λ or the presence of pS er218FoxO1. Moreover, suppression of aPKC λ expression or inhibition of its activity in HUVEC s 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 aPKC λ inhibitors could be a novel treatment strategy for CAS patients.