| Literature DB >> 32183950 |
Hong Liu1, Xinwei Kuang2, Yongchang Zhang3, Youqiong Ye4, Jialu Li5, Long Liang6, Zuozhong Xie7, Liang Weng8, Jia Guo9, Hui Li10, Fangyu Ma11, Xiaodan Chen9, Shuang Zhao9, Juan Su2, Nong Yang3, Fang Fang12, Yang Xie13, Juan Tao14, Jianglin Zhang7, Mingliang Chen7, Cong Peng9, Lunquan Sun8, Xin Zhang15, Jing Liu16, Leng Han17, Xiaowei Xu18, Mien-Chie Hung19, Xiang Chen20.
Abstract
Here, we show that tumor ADORA1 deletion suppresses cell growth in human melanoma cell lines in vitro and tumor development in vivo in immune-deficient xenografts. However, this deletion induces the upregulation of PD-L1 levels, which inactivates cocultured T cells in vitro, compromises anti-tumor immunity in vivo, and reduces anti-tumor efficacy in an immune-competent mouse model. Functionally, PD-1 mAb treatment enhances the efficacy of ADORA1-deficient or ADORA1 antagonist-treated melanoma and NSCLC immune-competent mouse models. Mechanistically, we identify ATF3 as the factor transcriptionally upregulating PD-L1 expression. Tumor ATF3 deletion improves the effect of ADORA1 antagonist treatment of melanoma and NSCLC xenografts. We observe higher ADORA1, lower ATF3, and lower PD-L1 expression levels in tumor tissues from nonresponders among PD-1 mAb-treated NSCLC patients.Entities:
Keywords: PD-L1/PD-1; adenosine A1 receptor; adenosine signaling; cAMP-dependent transcription factor 3; combination therapy; immune checkpoint; immunotherapy; melanoma; non-small cell lung cancer; tumor microenvironment
Year: 2020 PMID： 32183950 DOI： 10.1016/j.ccell.2020.02.006
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743