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

Hideya Onishi; Akiko Fujimura; Yasuhiro Oyama; Akio Yamasaki; Akira Imaizumi; Makoto Kawamoto; Mitsuo Katano; Masayo Umebayashi; Takashi Morisaki

doi:10.1016/j.cellimm.2016.08.003

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

Hideya Onishi, Akiko Fujimura, Yasuhiro Oyama, Akio Yamasaki, Akira Imaizumi, Makoto Kawamoto, Mitsuo Katano, Masayo Umebayashi, Takashi Morisaki

Advanced Medical Intiatives

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21 Citations (Scopus)

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.

Original language	English
Pages (from-to)	199-204
Number of pages	6
Journal	Cellular Immunology
Volume	310
DOIs	https://doi.org/10.1016/j.cellimm.2016.08.003
Publication status	Published - Dec 1 2016

All Science Journal Classification (ASJC) codes

Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cellimm.2016.08.003

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title = "Hedgehog signaling regulates PDL-1 expression in cancer cells to induce anti-tumor activity by activated lymphocytes",

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.",

author = "Hideya Onishi and Akiko Fujimura and Yasuhiro Oyama and Akio Yamasaki and Akira Imaizumi and Makoto Kawamoto and Mitsuo Katano and Masayo Umebayashi and Takashi Morisaki",

note = "Funding Information: We thank Ms Kaori Nomiyama for skillful technical assistance. This study was supported by JSPS KAKENHI Grant Number 15K10055 . Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

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doi = "10.1016/j.cellimm.2016.08.003",

language = "English",

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T1 - Hedgehog signaling regulates PDL-1 expression in cancer cells to induce anti-tumor activity by activated lymphocytes

AU - Onishi, Hideya

AU - Fujimura, Akiko

AU - Oyama, Yasuhiro

AU - Yamasaki, Akio

AU - Imaizumi, Akira

AU - Kawamoto, Makoto

AU - Katano, Mitsuo

AU - Umebayashi, Masayo

AU - Morisaki, Takashi

PY - 2016/12/1

Y1 - 2016/12/1

N2 - 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.

AB - 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.

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

Abstract

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