Innate immune signaling and regulation in cancer immunotherapy

A pre-existing T cell-inflamed tumor microenvironment has prognostic utility and also can be predictive for re- sponse to contemporary cancer immunotherapies. The generation of a spontaneous T cell response against tumor-as- sociated antigens depends on innate immune activation, which drives type I...

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Published inCell research Vol. 27; no. 1; pp. 96 - 108
Main Authors Corrales, Leticia, Matson, Vyara, Flood, Blake, Spranger, Stefani, Gajewski, Thomas F
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.01.2017
Nature Publishing Group
Subjects
631/250/1933
631/250/262
631/250/516
692/699/67/1059/2325
Biomedical and Life Sciences
Cell Biology
Dendritic Cells - immunology
Humans
Immunity, Innate
Immunotherapy
Life Sciences
Microbiota
Neoplasms - immunology
Neoplasms - therapy
Review
Signal Transduction
Tumors
T细胞
信号调节
先天免疫
免疫治疗
免疫激活剂
免疫疗法
树突状细胞
肿瘤免疫
STING
dendritic cells
innate immune signaling
cancer immunotherapy
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Summary:A pre-existing T cell-inflamed tumor microenvironment has prognostic utility and also can be predictive for re- sponse to contemporary cancer immunotherapies. The generation of a spontaneous T cell response against tumor-as- sociated antigens depends on innate immune activation, which drives type I interferon （IFN） production. Recent work has revealed a major role for the STING pathway of cytosolic DNA sensing in this process. This cascade of events contributes to the activation of Batf3-1ineage dendritic cells （DCs）, which appear to be central to anti-tumor immunity. Non-T cell-inflamed tumors lack chemokines for Batf3 DC recruitment, have few Batf3 DCs, and lack a type I IFN gene signature, suggesting that failed innate immune activation may be the ultimate cause for lack of spontaneous T cell activation and accumulation. With this information in hand, new strategies for triggering innate immune activation and Batf3 DC recruitment are being developed, including novel STING agonists for de novo im- mune priming. Ultimately, the successful development of effective innate immune activators should expand the frac- tion of patients that can respond to immunotherapies, such as with checkpoint blockade antibodies.
Bibliography:A pre-existing T cell-inflamed tumor microenvironment has prognostic utility and also can be predictive for re- sponse to contemporary cancer immunotherapies. The generation of a spontaneous T cell response against tumor-as- sociated antigens depends on innate immune activation, which drives type I interferon （IFN） production. Recent work has revealed a major role for the STING pathway of cytosolic DNA sensing in this process. This cascade of events contributes to the activation of Batf3-1ineage dendritic cells （DCs）, which appear to be central to anti-tumor immunity. Non-T cell-inflamed tumors lack chemokines for Batf3 DC recruitment, have few Batf3 DCs, and lack a type I IFN gene signature, suggesting that failed innate immune activation may be the ultimate cause for lack of spontaneous T cell activation and accumulation. With this information in hand, new strategies for triggering innate immune activation and Batf3 DC recruitment are being developed, including novel STING agonists for de novo im- mune priming. Ultimately, the successful development of effective innate immune activators should expand the frac- tion of patients that can respond to immunotherapies, such as with checkpoint blockade antibodies.
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innate immune signaling; cancer immunotherapy; dendritic cells; STING
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These two authors contributed equally to this work.
ISSN:1001-0602
1748-7838
DOI:10.1038/cr.2016.149