Open AccessPD ‐L1 expression is mainly regulated by interferon gamma associated with JAK ‐ STAT pathway in gastric cancer
Author(s) -
Mimura Kousaku,
Teh Jun Liang,
Okayama Hirokazu,
Shiraishi Kensuke,
Kua LeyFang,
Koh Vivien,
Smoot Duane T.,
Ashktorab Hassan,
Oike Takahiro,
Suzuki Yoshiyuki,
Fazreen Zul,
Asuncion Bernadette R.,
Shabbir Asim,
Yong WeiPeng,
So Jimmy,
Soong Richie,
Kono Koji
Publication year - 2018
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.13424
Subject(s) - cancer research , immunotherapy , programmed cell death , tumor microenvironment , interferon , interferon gamma , cancer cell , cancer immunotherapy , cytokine , cancer , biology , medicine , apoptosis , immunology , immune system , biochemistry , tumor cells
Despite multidisciplinary treatment for patients with advanced gastric cancer, their prognosis remains poor. Therefore, the development of novel therapeutic strategies is urgently needed, and immunotherapy utilizing anti‐programmed death 1/‐programmed death ligand‐1 mA b is an attractive approach. However, as there is limited information on how programmed death ligand‐1 is upregulated on tumor cells within the tumor microenvironment, we examined the mechanism of programmed death ligand‐1 regulation with a particular focus on interferon gamma in an in vitro setting and in clinical samples. Our in vitro findings showed that interferon gamma upregulated programmed death ligand‐1 expression on solid tumor cells through the JAK ‐signal transducer and activator of transcription pathway, and impaired the cytotoxicity of tumor antigen‐specific CTL against tumor cells. Following treatment of cells with anti‐programmed death ligand‐1 mA b after interferon gamma‐pre‐treatment, the reduced anti‐tumor CTL activity by interferon gamma reached a higher level than the non‐treatment control targets. In contrast, programmed death ligand‐1 expression on tumor cells also significantly correlated with epithelial‐mesenchymal transition phenotype in a panel of solid tumor cells. In clinical gastric cancer samples, tumor membrane programmed death ligand‐1 expression significantly positively correlated with the presence of CD 8‐positive T cells in the stroma and interferon gamma expression in the tumor. The results suggest that gastric cancer patients with high CD 8‐positive T‐cell infiltration may be more responsive to anti‐programmed death 1/‐programmed death ligand‐1 mA b therapy.