STING-Dependent Cytosolic DNA Sensing Promotes Radiation-Induced Type I Interferon-Dependent Antitumor Immunity in Immunogenic Tumors
Open accessAbstract
Ionizing radiation-mediated tumor regression depends on type I interferon (IFN) and the adaptive immune response, but several pathways control I IFN induction. Here, we demonstrate that adaptor protein STING, but not MyD88, is required for type I IFN-dependent antitumor effects of radiation. In dendritic cells (DCs), STING was required for IFN-? induction in response to irradiated-tumor cells. The cytosolic DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS) mediated sensing of irradiated-tumor cells in DCs. Moreover, STING was essential for radiation-induced adaptive immune responses, which relied on type I IFN signaling on DCs. Exogenous IFN-? treatment rescued the cross-priming by cGAS or STING-deficient DCs. Accordingly, activation of STING by a second messenger cGAMP administration enhanced antitumor immunity induced by radiation. Thus radiation-mediated antitumor immunity in immunogenic tumors requires a functional cytosolic DNA-sensing pathway and suggests that cGAMP treatment might provide a new strategy to improve radiotherapy.
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Initiation of an adaptive immune response to radiation therapy has been linked to STING-mediated IFN-β induction by dendritic cells.
“Similarly, initiation of an adaptive immune response to radiation therapy has been linked to STING-mediated IFN-β induction by dendritic cells45.”
From Epigenetic state determines the in vivo efficacy of STING agonist therapy (2023) · cites this paper as [45]
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Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway
Sun, L., Wu, J., Du, F., Chen, X., & Chen, Z. J. (2013) · Science · doi:10.1126/science.1232458 · Cited by 4,996 · see citing works
Self-citationSTING is an endoplasmic reticulum adaptor that facilitates innate immune signalling
Ishikawa, H., & Barber, G. N. (2008) · Nature · doi:10.1038/nature07317 · Cited by 3,576 · see citing works
Apetoh, L., Ghiringhelli, F., Tesniere, A., Obeid, M., Ortiz, C., Criollo, A., Mignot, G., Maiuri, M. C., Ullrich, E., Saulnier, P., et al. (2007) · Nature Medicine · doi:10.1038/nm1622 · Cited by 3,056 · cited 6× · see citing works
“In contrast, chemotherapeutic agents and anti-HER2 antibody treatments have previously been demonstrated to depend on a distinct immune mechanism to trigger adaptive immune responses (Apetoh et al., 2007; Park et al., 2010).”
BackgroundInfluentialSterile inflammation: sensing and reacting to damage
Chen, G. Y., & Nuñez, G. (2010) · Nature Reviews Immunology · doi:10.1038/nri2873 · Cited by 3,051 · see citing works
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 · see citing works
Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide
Lande, R., Gregorio, J., Facchinetti, V., Chatterjee, B., Wang, Y.-H., Homey, B., Cao, W., Wang, Y.-H., Su, B., Nestle, F. O., et al. (2007) · Nature · doi:10.1038/nature06116 · Cited by 1,910 · see citing works
The history of toll-like receptors - redefining innate immunity
O'Neill, L. A. J., Golenbock, D., & Bowie, A. G. (2013) · Nature reviews. Immunology · doi:10.1038/nri3446 · Cited by 1,765 · see citing works
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 · see citing works
The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity
Park, S., Jiang, Z., Mortenson, E. D., Deng, L., Radkevich-Brown, O., Yang, X., Sattar, H., Wang, Y., Brown, N. K., Greene, M., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.06.014 · Cited by 577 · see citing works
Self-citationStagg, J., Loi, S., Divisekera, U., Ngiow, S. F., Duret, H., Yagita, H., Teng, M. W., & Smyth, M. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016569108 · Cited by 496 · see citing works
Flagged first, then by citations
Research works printed but not linked: 33
- Ablasser A Schmid-Burgk JL Hemmerling I Horvath GL Schmidt T Latz E Hornung V Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP. Nature 2013 503 530 534 24077100 PMC4142317
- Ahn J Gutman D Saijo S Barber GN STING manifests self DNA-dependent inflammatory disease. Proc Natl Acad Sci U S A 2012 109 19386 19391 23132945 PMC3511090
- Begg AC Stewart FA Vens C Strategies to improve radiotherapy with targeted drugs. Nat Rev Cancer 2011 11 239 253 21430696
- Bernard JJ Cowing-Zitron C Nakatsuji T Muehleisen B Muto J Borkowski AW Martinez L Greidinger EL Yu BD Gallo RL Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. Nat Med 2012 18 1286 1290 22772463 PMC3812946
- Burdette DL Vance RE STING and the innate immune response to nucleic acids in the cytosol. Nat Immunol 2013 14 19 26 23238760
- Burnette BC Liang H Lee Y Chlewicki L Khodarev NN Weichselbaum RR Fu YX Auh SL The efficacy of radiotherapy relies upon induction of type i interferon-dependent innate and adaptive immunity. Cancer Res 2011 71 2488 2496 21300764 PMC3070872
- Chamilos G Gregorio J Meller S Lande R Kontoyiannis DP Modlin RL Gilliet M Cytosolic sensing of extracellular self-DNA transported into monocytes by the antimicrobial peptide LL37. Blood 2012 120 3699 3707 22927244 PMC3488884
- Chen H Sun H You F Sun W Zhou X Chen L Yang J Wang Y Tang H Guan Y Activation of STAT6 by STING is critical for antiviral innate immunity. Cell 2011 147 436 446 22000020
- Deng L Liang H Burnette B Beckett M Darga T Weichselbaum RR Fu YX Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest 2014 124 687 695 24382348 PMC3904601
- Desmet CJ Ishii KJ Nucleic acid sensing at the interface between innate and adaptive immunity in vaccination. Nat Rev Immunol 2012 12 479 491 22728526
- Diana J Simoni Y Furio L Beaudoin L Agerberth B Barrat F Lehuen A Crosstalk between neutrophils, B-1a cells and plasmacytoid dendritic cells initiates autoimmune diabetes. Nat Med 2013 19 65 73 23242473
- Gall A Treuting P Elkon KB Loo YM Gale M Jr. Barber GN Stetson DB Autoimmunity initiates in nonhematopoietic cells and progresses via lymphocytes in an interferon-dependent autoimmune disease. Immunity 2012 36 120 131 22284419 PMC3269499
- Gao P Ascano M Zillinger T Wang W Dai P Serganov AA Gaffney BL Shuman S Jones RA Deng L Structure-function analysis of STING activation by c[G(2′,5′)pA(3′,5′)p] and targeting by antiviral DMXAA. Cell 2013b 154 748 762 23910378 PMC4386733
- Gehrke N Mertens C Zillinger T Wenzel J Bald T Zahn S Tuting T Hartmann G Barchet W Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing. Immunity 2013 39 482 495 23993650
- Holm CK Jensen SB Jakobsen MR Cheshenko N Horan KA Moeller HB Gonzalez-Dosal R Rasmussen SB Christensen MH Yarovinsky TO Virus-cell fusion as a trigger of innate immunity dependent on the adaptor STING. Nat Immunol 2012 13 737 743 22706339 PMC3411909
- Iida N Dzutsev A Stewart CA Smith L Bouladoux N Weingarten RA Molina DA Salcedo R Back T Cramer S Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 2013 342 967 970 24264989 PMC6709532
- Ishii KJ Kawagoe T Koyama S Matsui K Kumar H Kawai T Uematsu S Takeuchi O Takeshita F Coban C Akira S TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines. Nature 2008 451 725 729 18256672
- Kono H Rock KL How dying cells alert the immune system to danger. Nat Rev Immunol 2008 8 279 289 18340345 PMC2763408
- Lahaye X Satoh T Gentili M Cerboni S Conrad C Hurbain I El Marjou A Lacabaratz C Lelievre JD Manel N The capsids of HIV-1 and HIV-2 determine immune detection of the viral cDNA by the innate sensor cGAS in dendritic cells. Immunity 2013 39 1132 1142 24269171
- Lee Y Auh SL Wang Y Burnette B Meng Y Beckett M Sharma R Chin R Tu T Weichselbaum RR Fu YX Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood 2009 114 589 595 19349616 PMC2713472
- Li XD Wu J Gao D Wang H Sun L Chen ZJ Pivotal roles of cGAS-cGAMP signaling in antiviral defense and immune adjuvant effects. Science 2013 341 1390 1394 23989956 PMC3863637
- Liang H Deng L Chmura S Burnette B Liadis N Darga T Beckett MA Lingen MW Witt M Weichselbaum RR Fu YX Radiation-induced equilibrium is a balance between tumor cell proliferation and T cell-mediated killing. J Immunol 2013 190 5874 5881 23630355 PMC3660450
- Liauw SL Connell PP Weichselbaum RR New paradigms and future challenges in radiation oncology: an update of biological targets and technology. Sci Transl Med 2013 5 173sr172 PMC3769139 23427246
- Lippmann J Muller HC Naujoks J Tabeling C Shin S Witzenrath M Hellwig K Kirschning CJ Taylor GA Barchet W Dissection of a type I interferon pathway in controlling bacterial intracellular infection in mice. Cell Microbiol 2011 13 1668 1682 21790939 PMC3196383
- Marichal T Ohata K Bedoret D Mesnil C Sabatel C Kobiyama K Lekeux P Coban C Akira S Ishii KJ DNA released from dying host cells mediates aluminum adjuvant activity. Nat Med 2011 17 996 1002 21765404
- Moeller BJ Cao Y Li CY Dewhirst MW Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules. Cancer Cell 2004 5 429 441 15144951
- Paludan SR Bowie AG Immune sensing of DNA. Immunity 2013 38 870 880 23706668 PMC3683625
- Postow MA Callahan MK Barker CA Yamada Y Yuan J Kitano S Mu Z Rasalan T Adamow M Ritter E Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med 2012 366 925 931 22397654 PMC3345206
- Sharma S DeOliveira RB Kalantari P Parroche P Goutagny N Jiang Z Chan J Bartholomeu DC Lauw F Hall JP Innate immune recognition of an AT-rich stem-loop DNA motif in the Plasmodium falciparum genome. Immunity 2011 35 194 207 21820332 PMC3162998
- Takeuchi O Akira S Pattern recognition receptors and inflammation. Cell 2010 140 805 820 20303872
- Wu J Chen ZJ Innate immune sensing and signaling of cytosolic nucleic acids. Annu Rev Immunol 2014 32 461 488 24655297
- Wu J Sun L Chen X Du F Shi H Chen C Chen ZJ Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 2013 339 826 830 23258412 PMC3855410
- Zhang X Shi H Wu J Sun L Chen C Chen ZJ Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Mol Cell 2013 51 226 235 23747010 PMC3808999
Cited by
Sorted by citations
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
Immunogenic cell death in cancer and infectious disease
Galluzzi, L., Buqué, A., Kepp, O., Zitvogel, L., & Kroemer, G. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2016.107 · Cited by 3,119 · see citing works
Regulation and function of the cGAS–STING pathway of cytosolic DNA sensing
Chen, Q., Sun, L., & Chen, Z. J. (2016) · Nature Immunology · doi:10.1038/ni.3558 · Cited by 2,333 · see citing works
Self-citationThe cGAS–STING pathway as a therapeutic target in inflammatory diseases
Decout, A., Katz, J. D., Venkatraman, S., & Ablasser, A. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00524-z · Cited by 2,309 · see citing works
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 · see citing works
DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity
Vanpouille-Box, C., Alard, A., Aryankalayil, M. J., Sarfraz, Y., Diamond, J. M., Schneider, R. J., Inghirami, G., Coleman, C. N., Formenti, S. C., & Demaria, S. (2017) · Nature Communications · doi:10.1038/ncomms15618 · Cited by 1,834 · see citing works
CD4+ T cell help in cancer immunology and immunotherapy
Borst, J., Ahrends, T., Bąbała, N., Melief, C. J. M., & Kastenmüller, W. (2018) · Nature Reviews Immunology · doi:10.1038/s41577-018-0044-0 · Cited by 1,585 · see citing works
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 · see citing works
Self-citationMitotic progression following DNA damage enables pattern recognition within micronuclei
Harding, S. M., Benci, J. L., Irianto, J., Discher, D. E., Minn, A. J., & Greenberg, R. A. (2017) · Nature · doi:10.1038/nature23470 · Cited by 1,508 · see citing works
DNA sensing by the cGAS–STING pathway in health and disease
Motwani, M., Pesiridis, S., & Fitzgerald, K. A. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0151-1 · Cited by 1,467 · see citing works
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 · see citing works
The cGAS–cGAMP–STING pathway connects DNA damage to inflammation, senescence, and cancer
Li, T., & Chen, Z. J. (2018) · Journal of Experimental Medicine · doi:10.1084/jem.20180139 · Cited by 1,293 · see citing works
Self-citationSTING: infection, inflammation and cancer.
Barber, G. N. (2015) · Nature Reviews Immunology · doi:10.1038/nri3921 · Cited by 1,313 · see citing works
Type I interferons in anticancer immunity
Zitvogel, L., Galluzzi, L., Kepp, O., Smyth, M. J., & Kroemer, G. (2015) · Nature Reviews Immunology · doi:10.1038/nri3845 · Cited by 1,305 · see citing works
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 · see citing works
“Genetic defects that compromise endogenous DNA metabolism or instances that trigger massive, synchronized accumulation of dead cells represent examples of this phenomenon 26 27 28, 29 30.”
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 · see citing works
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 · see citing works
Combination cancer immunotherapies tailored to the tumour microenvironment
Smyth, M. J., Ngiow, S. F., Ribas, A., & Teng, M. W. L. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.209 · Cited by 944 · see citing works
The role of myeloid cells in cancer therapies
Engblom, C., Pfirschke, C., & Pittet, M. J. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.54 · Cited by 788 · see citing works
Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade
Ishizuka, J. J., Manguso, R. T., Cheruiyot, C. K., Bi, K., Panda, A., Iracheta-Vellve, A., Miller, B. C., Du, P. P., Yates, K. B., Dubrot, J., et al. (2019) · Nature · doi:10.1038/s41586-018-0768-9 · Cited by 697 · see citing works
Challenges and Opportunities for Pancreatic Cancer Immunotherapy
Bear, A. S., Vonderheide, R. H., & O'Hara, M. H. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.08.004 · Cited by 674 · see citing works
Combination strategies to maximize the benefits of cancer immunotherapy
Zhu, S., Zhang, T., Zheng, L., Liu, H., Song, W., Liu, D., Li, Z., & Pan, C.-X. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01164-5 · Cited by 654 · see citing works
Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment
Lam, K. C., Araya, R. E., Huang, A., Chen, Q., Di Modica, M., Rodrigues, R. R., Lopès, A., Johnson, S. B., Schwarz, B., Bohrnsen, E., et al. (2021) · Cell · doi:10.1016/j.cell.2021.09.019 · Cited by 604 · see citing works
Xia, T., Konno, H., Ahn, J., & Barber, G. N. (2016) · Cell Reports · doi:10.1016/j.celrep.2015.12.029 · Cited by 589 · see citing works
PARP inhibition elicits STING-dependent antitumor immunity in brca1-deficient ovarian cancer
Ding, L., Kim, H.-J., Wang, Q., Kearns, M., Jiang, T., Ohlson, C. E., Li, B. B., Xie, S., Liu, J. F., Stover, E. H., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.054 · Cited by 572 · see citing works
Luke, J. J., Lemons, J. M., Karrison, T. G., Pitroda, S. P., Melotek, J. M., Zha, Y., Al-Hallaq, H. A., Arina, A., Khodarev, N. N., Janisch, L., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.76.2229 · Cited by 588 · see citing works
Self-citationcGAS is essential for the antitumor effect of immune checkpoint blockade
Wang, H., Hu, S., Chen, X., Shi, H., Chen, C., Sun, L., & Chen, Z. J. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1621363114 · Cited by 563 · see citing works
Self-citationBarkley, D., Moncada, R., Pour, M., Liberman, D. A., Dryg, I., Werba, G., Wang, W., Baron, M., Rao, A., Xia, B., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01141-9 · Cited by 532 · see citing works
Teo, M. Y., Seier, K., Ostrovnaya, I., Regazzi, A. M., Kania, B. E., Moran, M. M., Cipolla, C. K., Bluth, M. J., Chaim, J., Al-Ahmadie, H., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.75.7740 · Cited by 544 · see citing works
Recognition of Endogenous Nucleic Acids by the Innate Immune System
Roers, A., Hiller, B., & Hornung, V. (2016) · Immunity · doi:10.1016/j.immuni.2016.04.002 · Cited by 541 · see citing works
Magnitude of Therapeutic STING Activation Determines CD8+ T Cell-Mediated Anti-tumor Immunity
Sivick, K. E., Desbien, A. L., Glickman, L. H., Reiner, G. L., Corrales, L., Surh, N. H., Hudson, T. E., Vu, U. T., Francica, B. J., Banda, T., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.11.047 · Cited by 451 · see citing works
STING: a master regulator in the cancer-immunity cycle
Zhu, Y., An, X., Zhang, X., Qiao, Y., Zheng, T., & Li, X. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1087-y · Cited by 431 · see citing works
Self-citationLuo, X., Li, H., Ma, L., Zhou, J., Guo, X., Woo, S.-L., Pei, Y., Knight, L. R., Deveau, M., Chen, Y., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.09.010 · Cited by 415 · see citing works
Activating cGAS-STING pathway for the optimal effect of cancer immunotherapy
Li, A., Yi, M., Qin, S., Song, Y., Chu, Q., & Wu, K. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0721-x · Cited by 413 · see citing works
Innate immune signaling and regulation in cancer immunotherapy
Corrales, L., Matson, V., Flood, B., Spranger, S., & Gajewski, T. F. (2017) · Cell Research · doi:10.1038/cr.2016.149 · Cited by 408 · see citing works
Self-citationMcBride, S., Sherman, E., Tsai, C. J., Baxi, S., Aghalar, J., Eng, J., Zhi, W. I., McFarland, D., Michel, L. S., Young, R., et al. (2021) · Journal of Clinical Oncology · doi:10.1200/jco.20.00290 · Cited by 402 · see citing works
Stress-glucocorticoid-TSC22D3 axis compromises therapy-induced antitumor immunity
Yang, H., Xia, L., Chen, J., Zhang, S., Martin, V., Li, Q., Lin, S., Chen, J., Calmette, J., Lu, M., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0566-4 · Cited by 379 · see citing works
Molecular Mechanisms of Radiation-Induced Cancer Cell Death: A Primer
Sia, J., Szmyd, R., Hau, E., & Gee, H. E. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00041 · Cited by 378 · see citing works
SLC19A1 is an importer of the immunotransmitter cGAMP.
Ritchie, C., Cordova, A. F., Hess, G. T., Bassik, M. C., & Li, L. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.05.006 · Cited by 333 · see citing works
Uribe-Herranz, M., Rafail, S., Beghi, S., Gil-de-Gómez, L., Verginadis, I., Bittinger, K., Pustylnikov, S., Pierini, S., Perales-Linares, R., Blair, I. A., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci124332 · Cited by 316 · see citing works
Immunity, Hypoxia, and Metabolism–the Ménage à Trois of Cancer: Implications for Immunotherapy
Riera-Domingo, C., Audigé, A., Granja, S., Cheng, W.-C., Ho, P.-C., Baltazar, F., Stockmann, C., & Mazzone, M. (2020) · Physiological Reviews · doi:10.1152/physrev.00018.2019 · Cited by 310 · see citing works
Li, W., Lu, L., Lu, J., Wang, X., Yang, C., Jin, J., Wu, L., Hong, X., Li, F., Cao, D., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aay9013 · Cited by 305 · see citing works
Self-citationCD40 stimulation obviates innate sensors and drives T cell immunity in cancer
Byrne, K. T., & Vonderheide, R. H. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.058 · Cited by 282 · see citing works
Trial watch: STING agonists in cancer therapy
Le Naour, J., Zitvogel, L., Galluzzi, L., Vacchelli, E., & Kroemer, G. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1777624 · Cited by 289 · see citing works
DNA Sensing in Mismatch Repair-Deficient Tumor Cells Is Essential for Anti-tumor Immunity
Lu, C., Guan, J., Lu, S., Jin, Q., Rousseau, B., Lu, T., Stephens, D., Zhang, H., Zhu, J., Yang, M., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2020.11.006 · Cited by 285 · see citing works
Self-citationResearch Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response
Wan, D., Jiang, W., & Hao, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00615 · Cited by 270 · see citing works
Radiation therapy and anti-tumor immunity: exposing immunogenic mutations to the immune system
Lhuillier, C., Rudqvist, N.-P., Elemento, O., Formenti, S. C., & Demaria, S. (2019) · Genome Medicine · doi:10.1186/s13073-019-0653-7 · Cited by 276 · see citing works
DNA damage-induced type I interferon promotes senescence and inhibits stem cell function
Yu, Q., Katlinskaya, Y. V., Carbone, C. J., Zhao, B., Katlinski, K. V., Zheng, H., Guha, M., Li, N., Chen, Q., Yang, T., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.03.069 · Cited by 260 · see citing works
Cytosolic DNA Sensing in Organismal Tumor Control
Vanpouille-Box, C., Demaria, S., Formenti, S. C., & Galluzzi, L. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.05.013 · Cited by 250 · see citing works
Niraparib activates interferon signaling and potentiates anti-PD-1 antibody efficacy in tumor models
Wang, Z., Sun, K., Xiao, Y., Feng, B., Mikule, K., Ma, X., Feng, N., Vellano, C. P., Federico, L., Marszalek, J. R., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-38534-6 · Cited by 253 · see citing works
Trial watch: TLR3 agonists in cancer therapy
Le Naour, J., Galluzzi, L., Zitvogel, L., Kroemer, G., & Vacchelli, E. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1771143 · Cited by 239 · see citing works
Dinaciclib induces immunogenic cell death and enhances anti-PD1-mediated tumor suppression
Hossain, D. M. S., Javaid, S., Cai, M., Zhang, C., Sawant, A., Hinton, M., Sathe, M., Grein, J., Blumenschein, W., Pinheiro, E. M., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci94586 · Cited by 216 · see citing works
Role of the cGAS–STING pathway in cancer development and oncotherapeutic approaches
Khoo, L. T., & Chen, L. (2018) · The EMBO Reports · doi:10.15252/embr.201846935 · Cited by 204 · see citing works
Yang, Y., Wu, M., Cao, D., Yang, C., Jin, J., Wu, L., Hong, X., Li, W., Lu, L., Li, J., et al. (2021) · Science Advances · doi:10.1126/sciadv.abf6290 · Cited by 187 · see citing works
Self-citationPharmacological modulation of nucleic acid sensors - therapeutic potential and persisting obstacles
Vanpouille-Box, C., Hoffmann, J. A., & Galluzzi, L. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0043-2 · Cited by 183 · see citing works
p53 engages the cGAS/STING cytosolic DNA sensing pathway for tumor suppression
Ghosh, M., Saha, S., Li, J., Montrose, D. C., & Martinez, L. A. (2023) · Molecular Cell · doi:10.1016/j.molcel.2022.12.023 · Cited by 166 · see citing works
Interferons and the immunogenic effects of cancer therapy
Minn, A. J. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.09.007 · Cited by 130 · see citing works
Type I interferons and dendritic cells in cancer immunotherapy
(2019) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2019.06.001 · Cited by 124 · see citing works
SENP3 senses oxidative stress to facilitate STING-dependent dendritic cell antitumor function
Hu, Z., Teng, X.-L., Zhang, T., Yu, X., Ding, R., Yi, J., Deng, L., Wang, Z., & Zou, Q. (2021) · Molecular Cell · doi:10.1016/j.molcel.2020.12.024 · Cited by 123 · see citing works
Self-citationCytosolic sensing of immuno-stimulatory DNA, the enemy within
Dhanwani, R., Takahashi, M., & Sharma, S. (2018) · Current Opinion in Immunology · doi:10.1016/j.coi.2017.11.004 · Cited by 123 · see citing works
Chen, J., Harding, S. M., Natesan, R., Tian, L., Benci, J. L., Li, W., Minn, A. J., Asangani, I. A., & Greenberg, R. A. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108080 · Cited by 111 · see citing works
Cytoplasmic Mechanisms of Recognition and Defense of Microbial Nucleic Acids
Hu, M.-M., & Shu, H.-B. (2018) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100617-062903 · Cited by 110 · see citing works
TBK1, a central kinase in innate immune sensing of nucleic acids and beyond
Zhou, R., Zhang, Q., & Xu, P. (2020) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmaa051 · Cited by 104 · see citing works
Assessing the future of solid tumor immunotherapy
Guha, P., Heatherton, K. R., O’Connell, K. P., Alexander, I. S., & Katz, S. C. (2022) · Biomedicines · doi:10.3390/biomedicines10030655 · Cited by 105 · see citing works
Epigenetic state determines the in vivo efficacy of STING agonist therapy
Falahat, R., Berglund, A., Perez-Villarroel, P., Putney, R. M., Hamaidi, I., Kim, S., Pilon-Thomas, S., Barber, G. N., & Mulé, J. J. (2023) · Nature Communications · doi:10.1038/s41467-023-37217-1 · Cited by 94 · see citing works
Type I IFN activating type I dendritic cells for antitumor immunity
Liang, Y., Hannan, R., & Fu, Y.-X. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-2564 · Cited by 91 · see citing works
Self-citationShort-term gain, long-term pain: the senescence life cycle and cancer
Chan, A. S. L., & Narita, M. (2019) · Genes & Development · doi:10.1101/gad.320937.118 · Cited by 80 · see citing works
The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy
Shi, C., Qin, K., Lin, A., Jiang, A., Cheng, Q., Liu, Z., Zhang, J., & Luo, P. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02469-0 · Cited by 85 · see citing works
Kashyap, A. S., Fernandez-Rodriguez, L., Zhao, Y., Monaco, G., Trefny, M. P., Yoshida, N., Martin, K., Sharma, A., Olieric, N., Shah, P., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.08.057 · Cited by 76 · see citing works
TANK-binding kinase 1 as a novel therapeutic target for viral diseases
Zhao, C., & Zhao, W. (2019) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2019.1601702 · Cited by 61 · see citing works
Reciprocal regulation of STING and TCR signaling by mTORC1 for T-cell activation and function
Imanishi, T., Unno, M., Kobayashi, W., Yoneda, N., Matsuda, S., Ikeda, K., Hoshii, T., Hirao, A., Miyake, K., Barber, G. N., et al. (2019) · Life Science Alliance · doi:10.26508/lsa.201800282 · Cited by 62 · see citing works
Li, K., Gong, Y., Qiu, D., Tang, H., Zhang, J., Yuan, Z., Huang, Y., Qin, Y., Ye, L., & Yang, Y. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-004006 · Cited by 58 · see citing works
Interferons: role in cancer therapy
Abdolvahab, M. H., Darvishi, B., Zarei, M., Majidzadeh-A, K., & Farahmand, L. (2020) · Immunotherapy · doi:10.2217/imt-2019-0217 · Cited by 50 · see citing works
Targeting DNA Damage Response and Immune Checkpoint for Anticancer Therapy
Huang, J.-L., Chang, Y.-T., Hong, Z.-Y., & Lin, C.-S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063238 · Cited by 42 · see citing works
Yu, B., Lu, X., Feng, X., Zhao, T., Li, J., Lu, Y., Ye, F., Liu, X., Zheng, X., Shen, Z., et al. (2023) · International Journal of Nanomedicine · doi:10.2147/ijn.s428044 · Cited by 23 · see citing works
Wang, Y., Luo, W., Wang, X., Ma, Y., Huang, L., & Wang, Y. (2022) · Journal of Infection · doi:10.1016/j.jinf.2021.12.004 · Cited by 17 · see citing works
Alshebremi, M., Tomchuck, S. L., Myers, J. T., Kingsley, D. T., Eid, S., Abiff, M., Bonner, M., Saab, S. T., Choi, S. H., & Huang, A. Y.-C. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-006608 · Cited by 14 · see citing works
- Authors
- Deng, L., Liang, H., Xu, M., Yang, X., Burnette, B., Arina, A., Li, X.-D., Mauceri, H., Beckett, M., Darga, T., Huang, X., Gajewski, T. F., Chen, Z. J., Fu, Y.-X., & Weichselbaum, R. R.
- Affiliations
- University of Chicago (US)
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Fu, Yang-Xin
- Weichselbaum, Ralph R.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 41
- Issue
- 5
- Pages
- 843-852
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC5155593
- OpenAlex
- W1994826332
- Cited by
- 2,182
- References
- 10
- Citations by year
- 2026: 270 · 2025: 218 · 2024: 227 · 2023: 272 · 2022: 227 · 2021: 231 · 2020: 212 · 2019: 164 · 2018: 129 · 2017: 106 · 2016: 75 · 2015: 47 · 2014: 2 · 2013: 1
- FWCI
- 35.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA141975, CA111423, R01CA111423, R01CA141975, R01CA181160, R01CA134563, CA134563)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- STING, cytosolic DNA sensing, type I interferon, interferon-beta, dendritic cells, cGAS, cGAMP, immunogenic tumors, radiotherapy, cross-priming, MyD88, adaptive immune response
- MeSH terms
- STING Protein, Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase, Animals, Antineoplastic Agents, Cells, Cultured, Dendritic Cells, DNA, Immunity, Innate, Membrane Proteins, Mice, Inbred C57BL, Neoplasms, Nucleotides, Cyclic, Nucleotidyltransferases, Radiation, Ionizing, Signal Transduction, Interferon-beta, Mice, Knockout, Adaptor Proteins, Vesicular Transport, RNA Interference, RNA, Small Interfering, Xanthones, Cross-Priming, Mice, Myeloid Differentiation Factor 88, Receptor, Interferon alpha-beta, Adaptive Immunity
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