STING, DCs and the link between innate and adaptive tumor immunity

• Published in: Molecular immunology Vol. 110; pp. 13 - 23
• Main Authors: Vatner, Ralph E., Janssen, Edith M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-06-2019
• Subjects: Adaptive Immunity - physiology; Animals; Antigens, Neoplasm - genetics; Antigens, Neoplasm - physiology; Cancer immunotherapy; Dendritic cell; Dendritic Cells - physiology; Humans; Immunity, Innate - physiology; Interferon; Interferons - genetics; Neoplasms - genetics; Neoplasms - immunology; Neoplasms - pathology; Radiation therapy; Signal Transduction - physiology; STING; Tumor Escape - genetics; Tumor Escape - immunology; Tumor immunity; Dendritic cell; STING; Interferon; Tumor immunity; Radiation therapy; Cancer immunotherapy
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2017.12.001

•Dendritic cells (DCs) serve as the cellular link between innate and adaptive anti-tumor immunity.•DCs are essential for cross-priming adaptive T cell responses against tumors.•STING-mediated Type I IFN induction in DCs is essential for spontaneous and therapy induced anti-tumor T cell responses.•DNA released by cancer cells is the stimulus for generating tumor immunity through the STING/Interferon pathway.
Cancer and the immune system are intimately related. Much of the bulk of tumors is comprised of stromal leukocytes with immune functions, which serve to both promote and inhibit tumor growth, invasion and metastasis. The T lymphocytes of the adaptive immune system are essential for tumor immunity, and these T cells are generated by cross-priming against tumor associated antigens. Dendritic cells (DCs) are essential in this process, serving as the cellular link between innate and adaptive immunity. As a prerequisite for priming of adaptive immune responses, DCs must take up tumor antigens, process them and present them in the context of the major histocompatibility complex (MHC). DCs also serve as sensors of innate activation signals from cancer that are necessary for their activation and effective priming of cancer specific T cells. Here we discuss the role of DCs in the sensing of cancer and in priming the adaptive response against tumors. Furthermore, we present the essential role of the Stimulator of Interferon Genes (STING) signaling pathway in producing type I interferons (IFNs) that are essential in this process.