Hedgehog signaling regulates PDL-1 expression in cancer cells to induce anti-tumor activity by activated lymphocytes
Hedgehog signaling regulates PDL-1 expression in cancer cells to induce anti-tumor activity by activated lymphocytes
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DOI：
10.1016/j.cellimm.2016.08.003
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发表时间：
2016-12-01
影响因子：
4.3
通讯作者：
Morisaki, Takashi
中科院分区：
文献类型：
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作者：
Onishi, Hideya;Fujimura, Akiko;Morisaki, Takashi
我们研究了缺氧诱导的 Hh 信号激活是否有助于癌症中 PDL-1 的表达，以及它是否影响激活淋巴细胞的抗肿瘤功能。缺氧会增强 PDL-1 的表达，而抑制 Hh 信号会降低缺氧下 PDL-1 的表达。当活化的淋巴细胞与用 Hh 抑制剂治疗的癌症共培养时，活化的淋巴细胞数量在缺氧下增加。相反，当癌细胞用 PDL-1 中和抗体处理时，这种增加就被消除了。这些结果表明Hh信号是缺氧条件下PDL-1表达的调节途径之一，抑制Hh信号可能诱导淋巴细胞抗肿瘤活性。 (C) 2016 Elsevier Inc. 保留所有权利。
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. (C) 2016 Elsevier Inc. All rights reserved.