%0 Journal Article
%T PD©\L1 expression enhancement by infiltrating macrophage©\derived tumor necrosis factor©\¦Á leads to poor pancreatic cancer prognosis
%A Akira Chikamoto
%A Hideo Baba
%A Hirohisa Okabe
%A Katsunori Imai
%A Kota Arima
%A Masahiko Hirota
%A Masayo Tsukamoto
%A Naoki Umezaki
%A Shigeki Nakagawa
%A Takanobu Yamao
%A Takatoshi Ishiko
%A Takatsugu Ishimoto
%A Tatsunori Miyata
%A Yoshifumi Baba
%A Yoshihiro Komohara
%A Yo©\ichi Yamashita
%A Yuki Kitano
%J Archive of "Cancer Science".
%D 2019
%R 10.1111/cas.13874
%X Immunotherapy using anti©\PD©\1/PD©\L1 antibodies for several types of cancer has received considerable attention in recent decades. However, the molecular mechanism underlying PD©\L1 expression in pancreatic ductal adenocarcinoma (PDAC) cells has not been clearly elucidated. We investigated the clinical significance and regulatory mechanism of PD©\L1 expression in PDAC cells. Among the various cytokines tested, tumor necrosis factor (TNF)©\¦Á upregulated PD©\L1 expression in PDAC cells through NF©\¦ÊB signaling. The induction of PD©\L1 expression was also caused by co©\culture with activated macrophages, and the upregulation was inhibited by neutralization with anti©\TNF©\¦Á antibody after co©\culture with activated macrophages. PD©\L1 expression in PDAC cells was positively correlated with macrophage infiltration in tumor stroma of human PDAC tissues. In addition, survival analysis revealed that high PD©\L1 expression was significantly associated with poor prognosis in 235 PDAC patients and especially in patients harboring high CD8©\positive T©\cell infiltration. These findings indicate that tumor©\infiltrating macrophage©\derived TNF©\¦Á could be a potential therapeutic target for PDAC
%K macrophage
%K pancreatic cancer
%K PD©\L1
%K TNF©\¦Á
%K tumor stroma
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317925/