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.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Liu H,Kuang X,Zhang Y,Ye Y,Li J,Liang L,Xie Z,Weng L,Guo J,Li H,Ma F,Chen X,Zhao S,Su J,Yang N,Fang F,Xie Y,Tao J,Zhang J,Chen M,Peng C,Sun L,Zhang X,Liu J,Han L,Xu X,Hung MC,Chen Xdoi
10.1016/j.ccell.2020.02.006subject
Has Abstractpub_date
2020-03-16 00:00:00pages
324-339.e8issue
3eissn
1535-6108issn
1878-3686pii
S1535-6108(20)30095-7journal_volume
37pub_type
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