STING, DCs and the link between innate and adaptive tumor immunity
•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.•DN...
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| Published in: | Molecular immunology Vol. 110; pp. 13 - 23 |
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| Language: | English |
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01-06-2019
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| Abstract | •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. |
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| AbstractList | •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. 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. |
| Author | Vatner, Ralph E. Janssen, Edith M. |
| AuthorAffiliation | b Department of Radiation Oncology, University of Cincinnati College of Medicine, 234 Goodman Street, ML 0757, Cincinnati, OH 45267, United States a Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC 7038, Cincinnati, OH 45229, United States |
| AuthorAffiliation_xml | – name: b Department of Radiation Oncology, University of Cincinnati College of Medicine, 234 Goodman Street, ML 0757, Cincinnati, OH 45267, United States – name: a Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC 7038, Cincinnati, OH 45229, United States |
| Author_xml | – sequence: 1 givenname: Ralph E. surname: Vatner fullname: Vatner, Ralph E. email: Ralph.Vatner@UC.edu organization: Division of Immunobiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7038, Cincinnati, OH 45229, United States – sequence: 2 givenname: Edith M. surname: Janssen fullname: Janssen, Edith M. organization: Division of Immunobiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7038, Cincinnati, OH 45229, United States |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29273394$$D View this record in MEDLINE/PubMed |
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| Keywords | Dendritic cell STING Interferon Tumor immunity Radiation therapy Cancer immunotherapy |
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| Snippet | •Dendritic cells (DCs) serve as the cellular link between innate and adaptive anti-tumor immunity.•DCs are essential for cross-priming adaptive T cell... 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... |
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| SubjectTerms | 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 |
| Title | STING, DCs and the link between innate and adaptive tumor immunity |
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