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cGAS is essential for the antitumor effect of immune checkpoint blockade

2017; National Academy of Sciences; Volume: 114; Issue: 7 Linguagem: Inglês

10.1073/pnas.1621363114

1091-6490

Hua Wang, Shuiqing Hu, Xiang Chen, Heping Shi, Chuo Chen, Lijun Sun, Zhijian J. Chen,

RNA modifications and cancer

Significance The recent success of immune checkpoint blockades, such as the use of antibodies against CTLA4, PD-1, and PD-L1 in cancer therapies has reinvigorated the concept of intrinsic antitumor immunity, but how the immune system detects tumors and generates antitumor immunity is still not well understood. Here we showed that the PD-L1 blockade lost its antitumor effects in mice lacking the cytosolic DNA sensor cGAS, suggesting that cGAS is essential for intrinsic antitumor immunity. Further, we showed that the cGAS product cGAMP has strong antitumor effects, especially when it is combined with the PD-L1 antibody. These results demonstrate that cGAS plays a pivotal role in cancer immunity and that cGAMP and its derivatives may be used directly for cancer immunotherapy.