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Cell Immunol. 2016 Dec;310:199-204. doi: 10.1016/j.cellimm.2016.08.003. Epub 2016 Aug 8.

Hedgehog signaling regulates PDL-1 expression in cancer cells to induce anti-tumor activity by activated lymphocytes.

Author information

1
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: ohnishi@surg1.med.kyushu-u.ac.jp.
2
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
3
Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Shukoukai Inc., Tokyo, Japan.
4
Fukuoka General Cancer Clinic, Fukuoka, Japan.

Abstract

We investigated whether hypoxia-induced activation of Hh signaling contributes to PDL-1 expression in cancer and whether it affects the anti-tumor function of activated lymphocytes. Hypoxia augmented PDL-1 expression and inhibition of Hh signaling reduced PDL-1 expression under hypoxia. When activated lymphocytes were cocultured with cancers treated with a Hh inhibitor, activated lymphocyte cell numbers increased under hypoxia. In contrast, this increase was abrogated when cancer cells were treated with a PDL-1 neutralizing antibody. These results suggest that Hh signaling is one of regulatory pathways of PDL-1 expression under hypoxia and that inhibiting Hh signaling may induce lymphocyte anti-tumor activity.

KEYWORDS:

Activated lymphocytes; Hedgehog signaling; Hypoxia; PDL-1

PMID:
27522179
DOI:
10.1016/j.cellimm.2016.08.003
[Indexed for MEDLINE]

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