The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Tumor-Derived cGAMP Triggers a STING-Mediated Interferon Response in Non-tumor Cells to Activate the NK Cell Response
Open accessAbstract
Graphical Abstract Figure. No caption available. SUMMARY Detection of cytosolic DNA by the enzyme cGAS triggers the production of cGAMP, a second messenger that binds and activates the adaptor protein STING, which leads to interferon (IFN) production. Here, we found that in vivo natural killer (NK) cell killing of tumor cells, but not of normal cells, depends on STING expression in non‐tumor cells. Experiments using transplantable tumor models in STING‐ and cGAS‐deficient mice revealed that cGAS expression by tumor cells was critical for tumor rejection by NK cells. In contrast, cGAS expression by host cells was dispensable, suggesting that tumor‐derived cGAMP is transferred to non‐tumor cells, where it activates STING. cGAMP administration triggered STING activation and IFN‐&bgr; production in myeloid cells and B cells but not NK cells. Our results reveal that the anti‐tumor response of NK cells critically depends on the cytosolic DNA sensing pathway, similar to its role in defense against pathogens, and identify tumor‐derived cGAMP as a major determinant of tumor immunogenicity with implications for cancer immunotherapy. HIGHLIGHTSSting−/− mice, but not Cgas−/− mice, fail to mount optimal NK cell anti‐tumor responsesCgas−/− tumor cells are defective in inducing anti‐tumor responses by NK cellscGAS is constitutively active in tumor cells but not in untransformed cellscGAMP is transferred from tumor cells to other cells in the TME to activate STING &NA; Marcus et al. find that cGAMP produced by tumor cells triggers the activation of the STING pathway in immune cells within the tumor microenvironment. This leads to interferon production by these cells, which in turn activates NK cell anti‐tumor immunity.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Cerami, E., Gao, J., Dogrusoz, U., Gross, B. E., Sumer, S. O., Aksoy, B. A., Jacobsen, A., Byrne, C. J., Heuer, M. L., Larsson, E., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-12-0095 · Cited by 17,455
Wang, H., Yang, H., Shivalila, C. S., Dawlaty, M. M., Cheng, A. W., Zhang, F., & Jaenisch, R. (2013) · Cell · doi:10.1016/j.cell.2013.04.025 · Cited by 3,495
STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
Ishikawa, H., Ma, Z., & Barber, G. N. (2009) · Nature · doi:10.1038/nature08476 · Cited by 2,759 · cited 1×
“cGAMP binds and activates the endoplasmic reticulum (ER)-resident adaptor protein STING (stimulator of interferon genes protein) (Ablasser et al., 2013a; Diner et al., 2013; Gao et al., 2013c; Ishikawa et al., 2009; Zhang et al., 2013), which leads to the downstream activation of the transcription factors IFN regulato…”
CGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING.
Ablasser, A., Goldeck, M., Cavlar, T., Deimling, T., Witte, G., Röhl, I., Hopfner, K.-P., Ludwig, J., & Hornung, V. (2013) · Nature · doi:10.1038/nature12306 · Cited by 1,695
Corrales, L., Glickman, L. H., McWhirter, S. M., Kanne, D. B., Sivick, K. E., Katibah, G. E., Woo, S.-R., Lemmens, E., Banda, T., Leong, J. J., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.031 · Cited by 1,560
Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence
Glück, S., Guey, B., Gulen, M. F., Wolter, K., Kang, T.-W., Schmacke, N. A., Bridgeman, A., Rehwinkel, J., Zender, L., & Ablasser, A. (2017) · Nature Cell Biology · doi:10.1038/ncb3586 · Cited by 1,196
Gao, P., Ascano, M., Wu, Y., Barchet, W., Gaffney, B. L., Zillinger, T., Serganov, A. A., Liu, Y., Jones, R. A., Hartmann, G., et al. (2013) · Cell · doi:10.1016/j.cell.2013.04.046 · Cited by 1,101
Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity
Diefenbach, A., Jensen, E. R., Jamieson, A. M., & Raulet, D. H. (2001) · Nature · doi:10.1038/35093109 · Cited by 1,083
Self-citationHärtlova, A., Erttmann, S. F., Raffi, F. A., Schmalz, A. M., Resch, U., Anugula, S., Lienenklaus, S., Nilsson, L. M., Kröger, A., Nilsson, J. A., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.01.012 · Cited by 716
Xia, T., Konno, H., Ahn, J., & Barber, G. N. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.029 · Cited by 589
Cited by
Molecular mechanisms and cellular functions of cGAS–STING signalling
Hopfner, K.-P., & Hornung, V. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0244-x · Cited by 2,052
The Cytosolic DNA-Sensing cGAS–STING Pathway in Cancer
Kwon, J., & Bakhoum, S. F. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0761 · Cited by 1,293
Lv, M., Chen, M., Zhang, R., Zhang, W., Wang, C., Zhang, Y., Wei, X., Guan, Y., Liu, J., Feng, K., et al. (2020) · Cell Research · doi:10.1038/s41422-020-00395-4 · Cited by 1,040
Harnessing innate immunity in cancer therapy
Demaria, O., Cornen, S., Daëron, M., Morel, Y., Medzhitov, R., & Vivier, E. (2019) · Nature · doi:10.1038/s41586-019-1593-5 · Cited by 957
The cGAS–STING pathway and cancer
Samson, N., & Ablasser, A. (2022) · Nature Cancer · doi:10.1038/s43018-022-00468-w · Cited by 668
Metadata
- Authors
- Marcus, A., Mao, A. J., Lensink-Vasan, M., Wang, L., Vance, R. E., & Raulet, D. H.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 49
- Issue
- 4
- Pages
- 754-763.e4
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2897257669
- Cited by
- 611
- References
- 11
- FWCI
- 15.52
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Tumor-Derived cGAMP Triggers a STING-Mediated Interferon Response in Non-tumor Cells to Activate the NK Cell Response. https://app.cochat.ai/papers/10.1016/j.immuni.2018.09.016
- The paper
- Marcus, A., Mao, A. J., Lensink-Vasan, M., Wang, L., Vance, R. E., & Raulet, D. H. (2018). Tumor-Derived cGAMP Triggers a STING-Mediated Interferon Response in Non-tumor Cells to Activate the NK Cell Response. Immunity. https://doi.org/10.1016/j.immuni.2018.09.016
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
