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cGAS is essential for the antitumor effect of immune checkpoint blockade

Proceedings of the National Academy of Sciences - PNAS, 2017-02, Vol.114 (7), p.1637-1642 [Peer Reviewed Journal]

Volumes 1–89 and 106–114, copyright as a collective work only; author(s) retains copyright to individual articles ;Copyright National Academy of Sciences Feb 14, 2017 ;ISSN: 0027-8424 ;EISSN: 1091-6490 ;DOI: 10.1073/pnas.1621363114 ;PMID: 28137885

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  • Title:
    cGAS is essential for the antitumor effect of immune checkpoint blockade
  • Author: Wang, Hua ; Hu, Shuiqing ; Chen, Xiang ; Shi, Heping ; Chen, Chuo ; Sun, Lijun ; Chen, Zhijian J.
  • Subjects: Biological Sciences ; Effects ; Immune system ; Lymphocytes ; Molecules ; Rodents ; Tumors
  • Is Part Of: Proceedings of the National Academy of Sciences - PNAS, 2017-02, Vol.114 (7), p.1637-1642
  • Description: cGMP-AMP (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that activates innate immune responses. cGAS catalyzes the synthesis of cGAMP, which functions as a second messenger that binds and activates the adaptor protein STING to induce type I interferons (IFNs) and other immune modulatory molecules. Here we show that cGAS is indispensable for the antitumor effect of immune checkpoint blockade in mice. Wild-type, but not cGAS-deficient, mice exhibited slower growth of B16 melanomas in response to a PD-L1 antibody treatment. Consistently, intramuscular delivery of cGAMP inhibited melanoma growth and prolonged the survival of the tumor-bearing mice. The combination of cGAMP and PD-L1 antibody exerted stronger antitumor effects than did either treatment alone. cGAMP treatment activated dendritic cells and enhanced cross-presentation of tumor-associated antigens to CD8 T cells. These results indicate that activation of the cGAS pathway is important for intrinsic antitumor immunity and that cGAMP may be used directly for cancer immunotherapy.
  • Publisher: United States: National Academy of Sciences
  • Language: English
  • Identifier: ISSN: 0027-8424
    EISSN: 1091-6490
    DOI: 10.1073/pnas.1621363114
    PMID: 28137885
  • Source: Geneva Foundation Free Medical Journals at publisher websites
    PubMed Central
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