Hardy MP, Owczarek CM, Jermiin LS, Ejdebäck M, Hertzog PJ. Characterization of the type I interferon locus and identification of novel genes. Genomics. 2004;84:331–45.
Paludan SR, Pradeu T, Masters SL, Mogensen TH. Constitutive immune mechanisms: mediators of host defence and immune regulation. Nat Rev Immunol. 2021;21:137–50.
Vanpouille-Box C, Hoffmann JA, Galluzzi L. Pharmacological modulation of nucleic acid sensors – therapeutic potential and persisting Obstacles. Nat Rev Drug Discov. 2019;18:845–67.
Brubaker SW, Bonham KS, Zanoni I, Kagan JC. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol. 2015;33:257–90.
Lind NA, Rael VE, Pestal K, Liu B, Barton GM. Regulation of the nucleic acid-sensing Toll-like receptors. Nat Rev Immunol. 2022;22:224–35.
Rehwinkel J, Gack MU. RIG-I-like receptors: their regulation and roles in RNA sensing. Nat Rev Immunol. 2020;20:537–51.
Zhang Z, Zhang C. Regulation of cGAS-STING signalling and its diversity of cellular outcomes. Nat Rev Immunol. 2025;25:425–44.
Tenoever BR, Ng SL, Chua MA, McWhirter SM, García-Sastre A, Maniatis T. Multiple functions of the IKK-related kinase IKKepsilon in interferon-mediated antiviral immunity. Science. 2007;315:1274–8.
Müller M, Briscoe J, Laxton C, Guschin D, Ziemiecki A, Silvennoinen O, Harpur AG, Barbieri G, Witthuhn BA, Schindler C, et al. The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction. Nature. 1993;366:129–35.
Shuai K, Ziemiecki A, Wilks AF, Harpur AG, Sadowski HB, Gilman MZ, Darnell JE. Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and stat proteins. Nature. 1993;366:580–3.
Silvennoinen O, Ihle JN, Schlessinger J, Levy DE. Interferon-induced nuclear signalling by Jak protein tyrosine kinases. Nature. 1993;366:583–5.
Colamonici O, Yan H, Domanski P, Handa R, Smalley D, Mullersman J, Witte M, Krishnan K, Krolewski J. Direct binding to and tyrosine phosphorylation of the alpha subunit of the type I interferon receptor by p135tyk2 tyrosine kinase. Mol Cell Biol. 1994;14:8133–42.
Kessler DS, Veals SA, Fu XY, Levy DE. Interferon-alpha regulates nuclear translocation and DNA-binding affinity of ISGF3, a multimeric transcriptional activator. Genes Dev. 1990;4:1753–65.
Fu XY, Kessler DS, Veals SA, Levy DE, Darnell JE Jr. ISGF3, the transcriptional activator induced by interferon alpha, consists of multiple interacting polypeptide chains. Proc Natl Acad Sci U S A. 1990;87:8555–9.
Fu XY, Schindler C, Improta T, Aebersold R, Darnell JE Jr. The proteins of ISGF-3, the interferon alpha-induced transcriptional activator, define a gene family involved in signal transduction. Proc Natl Acad Sci U S A. 1992;89:7840–3.
Schindler C, Fu XY, Improta T, Aebersold R, Darnell JE Jr. Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. Proc Natl Acad Sci U S A. 1992;89:7836–9.
Schneider WM, Chevillotte MD, Rice CM. Interferon-stimulated genes: a complex web of host defenses. Annu Rev Immunol. 2014;32:513–45.
Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Nat Rev Immunol. 2014;14:36–49.
Samarajiwa SA, Forster S, Auchettl K, Hertzog PJ. INTERFEROME: the database of interferon regulated genes. Nucleic Acids Res. 2009;37:D852–857.
Porritt RA, Hertzog PJ. Dynamic control of type I IFN signalling by an integrated network of negative regulators. Trends Immunol. 2015;36:150–60.
Yamazaki T, Kirchmair A, Sato A, Buque A, Rybstein M, Petroni G, Bloy N, Finotello F, Stafford L, Navarro Manzano E, et al. Mitochondrial DNA drives abscopal responses to radiation that are inhibited by autophagy. Nat Immunol. 2020;21:1160–71.
Bartsch K, Knittler K, Borowski C, Rudnik S, Damme M, Aden K, Spehlmann ME, Frey N, Saftig P, Chalaris A, Rabe B. Absence of RNase H2 triggers generation of Immunogenic micronuclei removed by autophagy. Hum Mol Genet. 2017;26:3960–72.
Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI, Deretic V. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell. 2004;119:753–66.
Lindqvist LM, Frank D, McArthur K, Dite TA, Lazarou M, Oakhill JS, Kile BT, Vaux DL. Autophagy induced during apoptosis degrades mitochondria and inhibits type I interferon secretion. Cell Death Differ. 2018;25:784–96.
Stetson DB, Ko JS, Heidmann T, Medzhitov R. Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell. 2008;134:587–98.
Mannion NM, Greenwood SM, Young R, Cox S, Brindle J, Read D, Nellåker C, Vesely C, Ponting CP, McLaughlin PJ, et al. The RNA-editing enzyme ADAR1 controls innate immune responses to RNA. Cell Rep. 2014;9:1482–94.
Song MM, Shuai K. The suppressor of cytokine signaling (SOCS) 1 and SOCS3 but not SOCS2 proteins inhibit interferon-mediated antiviral and antiproliferative activities. J Biol Chem. 1998;273:35056–62.
Kinjyo I, Hanada T, Inagaki-Ohara K, Mori H, Aki D, Ohishi M, Yoshida H, Kubo M, Yoshimura A. SOCS1/JAB is a negative regulator of LPS-induced macrophage activation. Immunity. 2002;17:583–91.
Malakhova OA, Yan M, Malakhov MP, Yuan Y, Ritchie KJ, Kim KI, Peterson LF, Shuai K, Zhang DE. Protein isgylation modulates the JAK-STAT signaling pathway. Genes Dev. 2003;17:455–60.
Jové V, Wheeler H, Lee CW, Healy DR, Levine K, Ralph EC, Yamaguchi M, Jiang ZK, Cabral E, Xu Y, et al. Type I interferon regulation by USP18 is a key vulnerability in cancer. iScience. 2024;27:109593.
Hida S, Ogasawara K, Sato K, Abe M, Takayanagi H, Yokochi T, Sato T, Hirose S, Shirai T, Taki S, Taniguchi T. CD8(+) T cell-mediated skin disease in mice lacking IRF-2, the transcriptional attenuator of interferon-alpha/beta signaling. Immunity. 2000;13:643–55.
Faget J, Biota C, Bachelot T, Gobert M, Treilleux I, Goutagny N, Durand I, Léon-Goddard S, Blay JY, Caux C, Ménétrier-Caux C. Early detection of tumor cells by innate immune cells leads to T(reg) recruitment through CCL22 production by tumor cells. Cancer Res. 2011;71:6143–52.
Rusinova I, Forster S, Yu S, Kannan A, Masse M, Cumming H, Chapman R, Hertzog PJ. Interferome v2.0: an updated database of annotated interferon-regulated genes. Nucleic Acids Res. 2013;41:D1040–1046.
Boukhaled GM, Harding S, Brooks DG. Opposing roles of type I interferons in cancer immunity. Annu Rev Pathol. 2021;16:167–98.
Vanpouille-Box C, Demaria S, Formenti SC, Galluzzi L. Cytosolic DNA sensing in organismal tumor control. Cancer Cell. 2018;34:361–78.
Holicek P, Guilbaud E, Klapp V, Truxova I, Spisek R, Galluzzi L, Fucikova J. Type I interferon and cancer. Immunol Rev. 2024;321:115–27.
Zitvogel L, Galluzzi L, Kepp O, Smyth MJ, Kroemer G. Type I interferons in anticancer immunity. Nat Rev Immunol. 2015;15:405–14.
Kureshi CT, Dougan SK. Cytokines in cancer. Cancer Cell. 2025;43:15–35.
Petroni G, Buqué A, Coussens LM, Galluzzi L. Targeting oncogene and non-oncogene addiction to inflame the tumour microenvironment. Nat Rev Drug Discov. 2022;21:440–62.
Galluzzi L, Guilbaud E, Schmidt D, Kroemer G, Marincola FM. Targeting Immunogenic cell stress and death for cancer therapy. Nat Rev Drug Discov. 2024;23:445–60.
Landolfo S, Guarini A, Riera L, Gariglio M, Gribaudo G, Cignetti A, Cordone I, Montefusco E, Mandelli F, Foa R. Chronic myeloid leukemia cells resistant to interferon-alpha lack STAT1 expression. Hematol J. 2000;1:7–14.
Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, Torrejon DY, Abril-Rodriguez G, Sandoval S, Barthly L, et al. Mutations associated with acquired resistance to PD-1 Blockade in melanoma. N Engl J Med. 2016;375:819–29.
Shin DS, Zaretsky JM, Escuin-Ordinas H, Garcia-Diaz A, Hu-Lieskovan S, Kalbasi A, Grasso CS, Hugo W, Sandoval S, Torrejon DY, et al. Primary resistance to PD-1 Blockade mediated by JAK1/2 mutations. Cancer Discov. 2017;7:188–201.
Chin YE, Kitagawa M, Su WC, You ZH, Iwamoto Y, Fu XY. Cell growth arrest and induction of cyclin-dependent kinase inhibitor p21 WAF1/CIP1 mediated by STAT1. Science. 1996;272:719–22.
Kuniyasu H, Yasui W, Kitahara K, Naka K, Yokozaki H, Akama Y, Hamamoto T, Tahara H, Tahara E. Growth inhibitory effect of interferon-beta is associated with the induction of cyclin-dependent kinase inhibitor p27Kip1 in a human gastric carcinoma cell line. Cell Growth Differ. 1997;8:47–52.
Sangfelt O, Erickson S, Einhorn S, Grandér D. Induction of Cip/Kip and Ink4 Cyclin dependent kinase inhibitors by interferon-alpha in hematopoietic cell lines. Oncogene. 1997;14:415–23.
Huang YF, Wee S, Gunaratne J, Lane DP, Bulavin DV. Isg15 controls p53 stability and functions. Cell Cycle. 2014;13:2200–10.
Forys JT, Kuzmicki CE, Saporita AJ, Winkeler CL, Maggi LB Jr., Weber JD. ARF and p53 coordinate tumor suppression of an oncogenic IFN-β-STAT1-ISG15 signaling axis. Cell Rep. 2014;7:514–26.
Selleri C, Sato T, Del Vecchio L, Luciano L, Barrett AJ, Rotoli B, Young NS, Maciejewski JP. Involvement of Fas-mediated apoptosis in the inhibitory effects of interferon-alpha in chronic myelogenous leukemia. Blood. 1997;89:957–64.
Gisslinger H, Kurzrock R, Gisslinger B, Jiang S, Li S, Virgolini I, Woloszczuk W, Andreeff M, Talpaz M. Autocrine cell suicide in a Burkitt lymphoma cell line (Daudi) induced by interferon alpha: involvement of tumor necrosis factor as ligand for the CD95 receptor. Blood. 2001;97:2791–7.
Chen Q, Gong B, Mahmoud-Ahmed AS, Zhou A, Hsi ED, Hussein M, Almasan A. Apo2L/TRAIL and Bcl-2-related proteins regulate type I interferon-induced apoptosis in multiple myeloma. Blood. 2001;98:2183–92.
de Luján Alvarez M, Cerliani JP, Monti J, Carnovale C, Ronco MT, Pisani G, Lugano MC, Carrillo MC. The in vivo apoptotic effect of interferon alfa-2b on rat preneoplastic liver involves Bax protein. Hepatology. 2002;35:824–33.
Schiavoni G, Sistigu A, Valentini M, Mattei F, Sestili P, Spadaro F, Sanchez M, Lorenzi S, D’Urso MT, Belardelli F, et al. Cyclophosphamide synergizes with type I interferons through systemic dendritic cell reactivation and induction of Immunogenic tumor apoptosis. Cancer Res. 2011;71:768–78.
Bernardo AR, Cosgaya JM, Aranda A, Jiménez-Lara AM. Synergy between RA and TLR3 promotes type I IFN-dependent apoptosis through upregulation of TRAIL pathway in breast cancer cells. Cell Death Dis. 2013;4:e479.
Jin WJ, Zangl LM, Hyun M, Massoud E, Schroeder K, Alexandridis RA, et al. ATM inhibition augments type I interferon response and antitumor T-cell immunity when combined with radiation therapy in murine tumor models. J Immunother Cancer. 2023;11:e007474.
Huber M, Suprunenko T, Ashhurst T, Marbach F, Raifer H, Wolff S, Strecker T, Viengkhou B, Jung SR, Obermann HL, et al. IRF9 prevents CD8(+) T cell exhaustion in an extrinsic manner during acute lymphocytic choriomeningitis virus infection. J Virol. 2017;91:e01219–01217.
Crouse J, Bedenikovic G, Wiesel M, Ibberson M, Xenarios I, Von Laer D, et al. Type I interferons protect T cells against NK cell attack mediated by the activating receptor NCR1. Immunity. 2014;40:961–73.
Nicolai CJ, Wolf N, Chang IC, Kirn G, Marcus A, Ndubaku CO, et al. NK cells mediate clearance of CD8(+) T cell-resistant tumors in response to STING agonists. Sci Immunol. 2020;5:eaaz2738.
Brodeur MN, Dopeso H, Zhu Y, Longhini ALF, Gazzo A, Sun S, et al. Interferon response and epigenetic modulation by SMARCA4 mutations drive ovarian tumor immunogenicity. Sci Adv. 2024;10:eadk4851.
Dufva O, Gandolfi S, Huuhtanen J, Dashevsky O, Duàn H, Saeed K, Klievink J, Nygren P, Bouhlal J, Lahtela J, et al. Single-cell functional genomics reveals determinants of sensitivity and resistance to natural killer cells in blood cancers. Immunity. 2023;56:2816–e28352813.
Diamond MS, Kinder M, Matsushita H, Mashayekhi M, Dunn GP, Archambault JM, et al. Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J Exp Med. 2011;208:1989–2003.
Cauwels A, Van Lint S, Paul F, Garcin G, De Koker S, Van Parys A, Wueest T, Gerlo S, Van der Heyden J, Bordat Y, et al. Delivering type I interferon to dendritic cells empowers tumor eradication and immune combination treatments. Cancer Res. 2018;78:463–74.
Pantel A, Teixeira A, Haddad E, Wood EG, Steinman RM, Longhi MP. Direct type i IFN but not MDA5/TLR3 activation of dendritic cells is required for maturation and metabolic shift to glycolysis after poly IC stimulation. PLoS Biol. 2014;12:e1001759.
Wu D, Sanin DE, Everts B, Chen Q, Qiu J, Buck MD, et al. Type 1 interferons induce changes in core metabolism that are critical for immune function. Immunity. 2016;44:1325–36.
Longhi MP, Trumpfheller C, Idoyaga J, Caskey M, Matos I, Kluger C, Salazar AM, Colonna M, Steinman RM. Dendritic cells require a systemic type I interferon response to mature and induce CD4 + Th1 immunity with Poly IC as adjuvant. J Exp Med. 2009;206:1589–602.
Luri-Rey C, Teijeira Á, Wculek SK, de Andrea C, Herrero C, Lopez-Janeiro A, Rodríguez-Ruiz ME, Heras I, Aggelakopoulou M, Berraondo P, et al. Cross-priming in cancer immunology and immunotherapy. Nat Rev Cancer. 2025;25:249–73.
Borst J, Ahrends T, Bąbała N, Melief CJM, Kastenmüller W. CD4(+) T cell help in cancer immunology and immunotherapy. Nat Rev Immunol. 2018;18:635–47.
Whitmore MM, DeVeer MJ, Edling A, Oates RK, Simons B, Lindner D, Williams BR. Synergistic activation of innate immunity by double-stranded RNA and CpG DNA promotes enhanced antitumor activity. Cancer Res. 2004;64:5850–60.
Reynolds MB, Klein B, McFadden MJ, Judge NK, Navarrete HE, Michmerhuizen BC, Awad D, Schultz TL, Harms PW, Zhang L, et al. Type I interferon governs immunometabolic checkpoints that coordinate inflammation during Staphylococcal infection. Cell Rep. 2024;43:114607.
Zemek RM, Chin WL, Fear VS, Wylie B, Casey TH, Forbes C, Tilsed CM, Boon L, Guo BB, Bosco A, et al. Temporally restricted activation of IFNbeta signaling underlies response to immune checkpoint therapy in mice. Nat Commun. 2022;13:4895.
Le Bon A, Durand V, Kamphuis E, Thompson C, Bulfone-Paus S, Rossmann C, Kalinke U, Tough DF. Direct stimulation of T cells by type I IFN enhances the CD8 + T cell response during cross-priming. J Immunol. 2006;176:4682–9.
Suthar MS, Ramos HJ, Brassil MM, Netland J, Chappell CP, Blahnik G, McMillan A, Diamond MS, Clark EA, Bevan MJ, Gale M Jr. The RIG-I-like receptor LGP2 controls CD8(+) T cell survival and fitness. Immunity. 2012;37:235–48.
Eriksen KW, Lovato P, Skov L, Krejsgaard T, Kaltoft K, Geisler C, Ødum N. Increased sensitivity to interferon-alpha in psoriatic T cells. J Invest Dermatol. 2005;125:936–44.
Lu C, Klement JD, Ibrahim ML, Xiao W, Redd PS, Nayak-Kapoor A, Zhou G, Liu K. Type I interferon suppresses tumor growth through activating the STAT3-granzyme B pathway in tumor-infiltrating cytotoxic T lymphocytes. J Immunother Cancer. 2019;7:157.
Starbeck-Miller GR, Xue HH, Harty JT. IL-12 and type I interferon prolong the division of activated CD8 T cells by maintaining high-affinity IL-2 signaling in vivo. J Exp Med. 2014;211:105–20.
Lacalle RA, Blanco R, Carmona-Rodríguez L, Martín-Leal A, Mira E, Mañes S. Chemokine receptor signaling and the hallmarks of cancer. Int Rev Cell Mol Biol. 2017;331:181–244.
Mowat C, Mosley SR, Namdar A, Schiller D, Baker K. Anti-tumor immunity in mismatch repair-deficient colorectal cancers requires type I IFN-driven CCL5 and CXCL10. J Exp Med. 2021;218:e20210108.
Gallucci S, Lolkema M, Matzinger P. Natural adjuvants: endogenous activators of dendritic cells. Nat Med. 1999;5:1249–55.
Galassi C, Chan TA, Vitale I, Galluzzi L. The hallmarks of cancer immune evasion. Cancer Cell. 2024;42:1825–63.
Gangaplara A, Martens C, Dahlstrom E, Metidji A, Gokhale AS, Glass DD, Lopez-Ocasio M, Baur R, Kanakabandi K, Porcella SF, Shevach EM. Type I interferon signaling attenuates regulatory T cell function in viral infection and in the tumor microenvironment. PLoS Pathog. 2018;14:e1006985.
Bacher N, Raker V, Hofmann C, Graulich E, Schwenk M, Baumgrass R, Bopp T, Zechner U, Merten L, Becker C, Steinbrink K. Interferon-α suppresses cAMP to disarm human regulatory T cells. Cancer Res. 2013;73:5647–56.
Yofe I, Landsberger T, Yalin A, Solomon I, Costoya C, Demane DF, Shah M, David E, Borenstein C, Barboy O, et al. Anti-CTLA-4 antibodies drive myeloid activation and reprogram the tumor microenvironment through FcγR engagement and type I interferon signaling. Nat Cancer. 2022;3:1336–50.
Togashi Y, Shitara K, Nishikawa H. Regulatory T cells in cancer immunosuppression – implications for anticancer therapy. Nat Rev Clin Oncol. 2019;16:356–71.
U’Ren L, Guth A, Kamstock D, Dow S. Type I interferons inhibit the generation of tumor-associated macrophages. Cancer Immunol Immunother. 2010;59:587–98.
Ming-Chin Lee K, Achuthan AA, De Souza DP, Lupancu TJ, Binger KJ, Lee MKS, Xu Y, McConville MJ, de Weerd NA, Dragoljevic D, et al. Type I interferon antagonism of the JMJD3-IRF4 pathway modulates macrophage activation and polarization. Cell Rep. 2022;39:110719.
Vitale I, Manic G, Coussens LM, Kroemer G, Galluzzi L. Macrophages and metabolism in the tumor microenvironment. Cell Metab. 2019;30:36–50.
Mantovani A, Allavena P, Marchesi F, Garlanda C. Macrophages as tools and targets in cancer therapy. Nat Rev Drug Discov. 2022;21:799–820.
Alicea-Torres K, Sanseviero E, Gui J, Chen J, Veglia F, Yu Q, Donthireddy L, Kossenkov A, Lin C, Fu S, et al. Immune suppressive activity of myeloid-derived suppressor cells in cancer requires inactivation of the type I interferon pathway. Nat Commun. 2021;12:1717.
Wan S, Pestka S, Jubin RG, Lyu YL, Tsai YC, Liu LF. Chemotherapeutics and radiation stimulate MHC class I expression through elevated interferon-beta signaling in breast cancer cells. PLoS ONE. 2012;7:e32542.
Sistigu A, Yamazaki T, Vacchelli E, Chaba K, Enot DP, Adam J, Vitale I, Goubar A, Baracco EE, Remedios C, et al. Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nat Med. 2014;20:1301–9.
Marchi S, Guilbaud E, Tait SWG, Yamazaki T, Galluzzi L. Mitochondrial control of inflammation. Nat Rev Immunol. 2023;23:159–73.
Anz D, Rapp M, Eiber S, Koelzer VH, Thaler R, Haubner S, Knott M, Nagel S, Golic M, Wiedemann GM, et al. Suppression of intratumoral CCL22 by type i interferon inhibits migration of regulatory T cells and blocks cancer progression. Cancer Res. 2015;75:4483–93.
Galluzzi L, Green DR. Autophagy-Independent functions of the autophagy machinery. Cell. 2019;177:1682–99.
Zhou H, Wang W, Xu H, Liang Y, Ding J, Lv M, Ren B, Peng H, Fu YX, Zhu M. Metabolic reprograming mediated by tumor cell-intrinsic type I IFN signaling is required for CD47-SIRPα Blockade efficacy. Nat Commun. 2024;15:5759.
Campisi M, Sundararaman SK, Shelton SE, Knelson EH, Mahadevan NR, Yoshida R, Tani T, Ivanova E, Cañadas I, Osaki T et al. Tumor-Derived cGAMP Regulates Activation of the Vasculature. Front Immunol. 2020, 11:2090.
Yang H, Lee WS, Kong SJ, Kim CG, Kim JH, Chang SK, Kim S, Kim G, Chon HJ, Kim C. STING activation reprograms tumor vasculatures and synergizes with VEGFR2 Blockade. J Clin Invest. 2019;129:4350–64.
Carmona-Rodríguez L, Martínez-Rey D, Fernández-Aceñero MJ, González-Martín A, Paz-Cabezas M, Rodríguez-Rodríguez N, Pérez-Villamil B, Sáez ME, Díaz-Rubio E, Mira E, Mañes S. SOD3 induces a HIF-2α-dependent program in endothelial cells that provides a selective signal for tumor infiltration by T cells. J Immunother Cancer. 2020;8:e000432.
Weichselbaum RR, Ishwaran H, Yoon T, Nuyten DS, Baker SW, Khodarev N, Su AW, Shaikh AY, Roach P, Kreike B, et al. An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer. Proc Natl Acad Sci U S A. 2008;105:18490–5.
Khodarev NN, Beckett M, Labay E, Darga T, Roizman B, Weichselbaum RR. STAT1 is overexpressed in tumors selected for radioresistance and confers protection from radiation in transduced sensitive cells. Proc Natl Acad Sci U S A. 2004;101:1714–9.
Khodarev NN, Roach P, Pitroda SP, Golden DW, Bhayani M, Shao MY, Darga TE, Beveridge MG, Sood RF, Sutton HG, et al. STAT1 pathway mediates amplification of metastatic potential and resistance to therapy. PLoS ONE. 2009;4:e5821.
Rodriguez-Ruiz ME, Buque A, Hensler M, Chen J, Bloy N, Petroni G, Sato A, Yamazaki T, Fucikova J, Galluzzi L. Apoptotic caspases inhibit abscopal responses to radiation and identify a new prognostic biomarker for breast cancer patients. Oncoimmunology. 2019;8:e1655964.
Kondratova AA, Cheon H, Dong B, Holvey-Bates EG, Hasipek M, Taran I, Gaughan C, Jha BK, Silverman RH, Stark GR. Suppressing parylation by 2’,5’-oligoadenylate synthetase 1 inhibits DNA damage-induced cell death. EMBO J. 2020;39:e101573.
Jacquelot N, Yamazaki T, Roberti MP, Duong CPM, Andrews MC, Verlingue L, Ferrere G, Becharef S, Vétizou M, Daillère R, et al. Sustained type I interferon signaling as a mechanism of resistance to PD-1 Blockade. Cell Res. 2019;29:846–61.
Benci JL, Xu B, Qiu Y, Wu TJ, Dada H, Twyman-Saint Victor C, Cucolo L, Lee DSM, Pauken KE, Huang AC, et al. Tumor interferon signaling regulates a Multigenic resistance program to immune checkpoint Blockade. Cell. 2016;167:1540–e15541512.
Bakhoum SF, Ngo B, Laughney AM, Cavallo JA, Murphy CJ, Ly P, Shah P, Sriram RK, Watkins TBK, Taunk NK, et al. Chromosomal instability drives metastasis through a cytosolic DNA response. Nature. 2018;553:467–72.
Hong C, Schubert M, Tijhuis AE, Requesens M, Roorda M, van den Brink A, Ruiz LA, Bakker PL, van der Sluis T, Pieters W, et al. cGAS-STING drives the IL-6-dependent survival of chromosomally instable cancers. Nature. 2022;607:366–73.
Li J, Hubisz MJ, Earlie EM, Duran MA, Hong C, Varela AA, Lettera E, Deyell M, Tavora B, Havel JJ, et al. Non-cell-autonomous cancer progression from chromosomal instability. Nature. 2023;620:1080–8.
Zeng Q, Yao C, Zhang S, Mao Y, Wang J, Wang Z, Sheng C, Chen S. ORMDL3 restrains type I interferon signaling and anti-tumor immunity by promoting RIG-I degradation. Elife. 2025;13:RP101973.
Lai P, Liu L, Bancaro N, Troiani M, Calì B, Li Y, Chen J, Singh PK, Arzola RA, Attanasio G, et al. Mitochondrial DNA released by senescent tumor cells enhances PMN-MDSC-driven immunosuppression through the cGAS-STING pathway. Immunity. 2025;58:811–e825817.
Chen J, Cao Y, Markelc B, Kaeppler J, Vermeer JA, Muschel RJ. Type I IFN protects cancer cells from CD8 + T cell-mediated cytotoxicity after radiation. J Clin Invest. 2019;129:4224–38.
Galassi C, Esteller M, Vitale I, Galluzzi L. Epigenetic control of immunoevasion in cancer stem cells. Trends Cancer. 2024;10:1052–71.
Qadir AS, Ceppi P, Brockway S, Law C, Mu L, Khodarev NN, Kim J, Zhao JC, Putzbach W, Murmann AE, et al. CD95/Fas increases stemness in cancer cells by inducing a STAT1-Dependent type I interferon response. Cell Rep. 2017;18:2373–86.
Musella M, Guarracino A, Manduca N, Galassi C, Ruggiero E, Potenza A, Maccafeo E, Manic G, Mattiello L, Soliman Abdel Rehim S, et al. Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B. Nat Immunol. 2022;23:1379–92.
Qiu J, Xu B, Ye D, Ren D, Wang S, Benci JL, Xu Y, Ishwaran H, Beltra JC, Wherry EJ, et al. Cancer cells resistant to immune checkpoint Blockade acquire interferon-associated epigenetic memory to sustain T cell dysfunction. Nat Cancer. 2023;4:43–61.
Kamada R, Yang W, Zhang Y, Patel MC, Yang Y, Ouda R, Dey A, Wakabayashi Y, Sakaguchi K, Fujita T, et al. Interferon stimulation creates chromatin marks and establishes transcriptional memory. Proc Natl Acad Sci U S A. 2018;115:E9162–71.
Cheon H, Wang Y, Wightman SM, Jackson MW, Stark GR. How cancer cells make and respond to interferon-I. Trends Cancer. 2023;9:83–92.
Rothenfusser S, Goutagny N, DiPerna G, Gong M, Monks BG, Schoenemeyer A, Yamamoto M, Akira S, Fitzgerald KA. The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I. J Immunol. 2005;175:5260–8.
Yonesaka K, Kurosaki T, Tanizaki J, Kawakami H, Tanaka K, Maenishi O, Takamura S, Sakai K, Chiba Y, Teramura T, et al. Chromosomal instability is associated with cGAS-STING activation in EGFR-TKI refractory Non-Small-Cell lung cancer. Cells. 2025;14:447.
Benci JL, Johnson LR, Choa R, Xu Y, Qiu J, Zhou Z, Xu B, Ye D, Nathanson KL, June CH, et al. Opposing functions of interferon coordinate adaptive and innate immune responses to cancer immune checkpoint Blockade. Cell. 2019;178:933–e948914.
Ma W, Oliveira-Nunes MC, Xu K, Kossenkov A, Reiner BC, Crist RC, Hayden J, Chen Q. Type I interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitment. Nat Commun. 2023;14:2632.
Dikopoulos N, Bertoletti A, Kröger A, Hauser H, Schirmbeck R, Reimann J. Type I IFN negatively regulates CD8 + T cell responses through IL-10-producing CD4 + T regulatory 1 cells. J Immunol. 2005;174:99–109.
Chen W, Teo JMN, Yau SW, Wong MY, Lok CN, Che CM, Javed A, Huang Y, Ma S, Ling GS. Chronic type I interferon signaling promotes lipid-peroxidation-driven terminal CD8(+) T cell exhaustion and curtails anti-PD-1 efficacy. Cell Rep. 2022;41:111647.
Fridman WH, Zitvogel L, Sautès-Fridman C, Kroemer G. The immune contexture in cancer prognosis and treatment. Nat Rev Clin Oncol. 2017;14:717–34.
Teijaro JR, Ng C, Lee AM, Sullivan BM, Sheehan KC, Welch M, Schreiber RD, de la Torre JC, Oldstone MB. Persistent LCMV infection is controlled by Blockade of type I interferon signaling. Science. 2013;340:207–11.
Wilson EB, Yamada DH, Elsaesser H, Herskovitz J, Deng J, Cheng G, Aronow BJ, Karp CL, Brooks DG. Blockade of chronic type I interferon signaling to control persistent LCMV infection. Science. 2013;340:202–7.
Mathew D, Marmarelis ME, Foley C, Bauml JM, Ye D, Ghinnagow R, Ngiow SF, Klapholz M, Jun S, Zhang Z, et al. Combined JAK Inhibition and PD-1 immunotherapy for non-small cell lung cancer patients. Science. 2024;384:eadf1329.
Zak J, Pratumchai I, Marro BS, Marquardt KL, Zavareh RB, Lairson LL, Oldstone MBA, Varner JA, Hegerova L, Cao Q, et al. JAK Inhibition enhances checkpoint Blockade immunotherapy in patients with hodgkin lymphoma. Science. 2024;384:eade8520.
Fu T, Jin X, He M, Chen YY, Yang YS, Chen L, Zhang HY, Fan L, Wu J, Wang ZH, et al. Interferon-induced senescent CD8(+) T cells reduce anti-PD1 immunotherapy efficacy in early triple-negative breast cancer. Sci Transl Med. 2025;17:eadj7808.
Galluzzi L, Smith KN, Liston A, Garg AD. The diversity of CD8(+) T cell dysfunction in cancer and viral infection. Nat Rev Immunol. 2025;25:662–79.
Mudla A, Jiang Y, Arimoto KI, Xu B, Rajesh A, Ryan AP, Wang W, Daugherty MD, Zhang DE, Hao N. Cell-cycle-gated feedback control mediates desensitization to interferon stimulation. Elife. 2020;9:e58825.
Kok F, Rosenblatt M, Teusel M, Nizharadze T, Gonçalves Magalhães V, Dächert C, Maiwald T, Vlasov A, Wäsch M, Tyufekchieva S, et al. Disentangling molecular mechanisms regulating sensitization of interferon alpha signal transduction. Mol Syst Biol. 2020;16:e8955.
Khodarev NN, Minn AJ, Efimova EV, Darga TE, Labay E, Beckett M, Mauceri HJ, Roizman B, Weichselbaum RR. Signal transducer and activator of transcription 1 regulates both cytotoxic and prosurvival functions in tumor cells. Cancer Res. 2007;67:9214–20.
Sung PS, Cheon H, Cho CH, Hong SH, Park DY, Seo HI, Park SH, Yoon SK, Stark GR, Shin EC. Roles of unphosphorylated ISGF3 in HCV infection and interferon responsiveness. Proc Natl Acad Sci U S A. 2015;112:10443–8.
Wang W, Yin Y, Xu L, Su J, Huang F, Wang Y, Boor PPC, Chen K, Wang W, Cao W, et al. Unphosphorylated ISGF3 drives constitutive expression of interferon-stimulated genes to protect against viral infections. Sci Signal. 2017;10:eaah4248.
Zierhut C, Yamaguchi N, Paredes M, Luo JD, Carroll T, Funabiki H. The cytoplasmic DNA sensor cGAS promotes mitotic cell death. Cell. 2019;178:302–e315323.
Vitale I, Shema E, Loi S, Galluzzi L. Intratumoral heterogeneity in cancer progression and response to immunotherapy. Nat Med. 2021;27:212–24.
Osokine I, Snell LM, Cunningham CR, Yamada DH, Wilson EB, Elsaesser HJ, de la Torre JC, Brooks D. Type I interferon suppresses de Novo virus-specific CD4 Th1 immunity during an established persistent viral infection. Proc Natl Acad Sci U S A. 2014;111:7409–14.
Cunningham CR, Champhekar A, Tullius MV, Dillon BJ, Zhen A, de la Fuente JR, Herskovitz J, Elsaesser H, Snell LM, Wilson EB, et al. Type I and type II interferon coordinately regulate suppressive dendritic cell fate and function during viral persistence. PLoS Pathog. 2016;12:e1005356.
Gebhardt T, Park SL, Parish IA. Stem-like exhausted and memory CD8(+) T cells in cancer. Nat Rev Cancer. 2023;23:780–98.
Broomfield BJ, Tan CW, Qin RZ, Abberger H, Duckworth BC, Alvarado C, Dalit L, Lee CL, Shandre Mugan R, Mazrad ZAI, et al. Transient Inhibition of type I interferon enhances CD8 + T cell stemness and vaccine protection. J Exp Med. 2025;222:e20241148.
Gauci L. Management of cancer patients receiving interferon alfa-2a. Int J Cancer Suppl. 1987;1:21–30.
Nassar D, Blanpain C. Cancer stem cells: basic concepts and therapeutic implications. Annu Rev Pathol. 2016;11:47–76.
Alcalá S, Sancho P, Martinelli P, Navarro D, Pedrero C, Martín-Hijano L, Valle S, Earl J, Rodríguez-Serrano M, Ruiz-Cañas L, et al. ISG15 and isgylation is required for pancreatic cancer stem cell mitophagy and metabolic plasticity. Nat Commun. 2020;11:2682.
Mills EL, Ryan DG, Prag HA, Dikovskaya D, Menon D, Zaslona Z, Jedrychowski MP, Costa ASH, Higgins M, Hams E, et al. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature. 2018;556:113–7.
Bourner LA, Chung LA, Long H, McGettrick AF, Xiao J, Roth K, Bailey JD, Strickland M, Tan B, Cunningham J, et al. Endogenously produced Itaconate negatively regulates innate-driven cytokine production and drives global ubiquitination in human macrophages. Cell Rep. 2024;43:114570.
Su C, Cheng T, Huang J, Zhang T, Yin H. 4-Octyl Itaconate restricts STING activation by blocking its palmitoylation. Cell Rep. 2023;42:113040.
O’Carroll SM, Peace CG, Toller-Kawahisa JE, Min Y, Hooftman A, Charki S, Kehoe L, O’Sullivan MJ, Zoller A, McGettrick AF, et al. Itaconate drives mtRNA-mediated type I interferon production through Inhibition of succinate dehydrogenase. Nat Metab. 2024;6:2060–9.
Van Eyndhoven LC, Singh A, Tel J. Decoding the dynamics of multilayered stochastic antiviral IFN-I responses. Trends Immunol. 2021;42:824–39.
Drayman N, Patel P, Vistain L, Tay S. HSV-1 single-cell analysis reveals the activation of anti-viral and developmental programs in distinct sub-populations. Elife. 2019;8:e46339.
Wimmers F, Subedi N, van Buuringen N, Heister D, Vivié J, Beeren-Reinieren I, Woestenenk R, Dolstra H, Piruska A, Jacobs JFM, et al. Single-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells. Nat Commun. 2018;9:3317.
Hoekstra ME, Bornes L, Dijkgraaf FE, Philips D, Pardieck IN, Toebes M, Thommen DS, van Rheenen J, Schumacher TNM. Long-distance modulation of bystander tumor cells by CD8(+) T cell-secreted IFNγ. Nat Cancer. 2020;1:291–301.
Thibaut R, Bost P, Milo I, Cazaux M, Lemaître F, Garcia Z, Amit I, Breart B, Cornuot C, Schwikowski B, Bousso P. Bystander IFN-γ activity promotes widespread and sustained cytokine signaling altering the tumor microenvironment. Nat Cancer. 2020;1:302–14.
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;71:2488–96.
Vanpouille-Box C, Alard A, Aryankalayil MJ, Sarfraz Y, Diamond JM, Schneider RJ, Inghirami G, Coleman CN, Formenti SC, Demaria S. DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nat Commun. 2017;8:15618.
Deng L, Liang H, Xu M, Yang X, Burnette B, Arina A, Li XD, Mauceri H, Beckett M, Darga T, et al. STING-Dependent cytosolic DNA sensing promotes Radiation-Induced type I Interferon-Dependent antitumor immunity in Immunogenic tumors. Immunity. 2014;41:843–52.
Klionsky DJ, Petroni G, Amaravadi RK, Baehrecke EH, Ballabio A, Boya P, Bravo-San Pedro JM, Cadwell K, Cecconi F, Choi AMK, et al. Autophagy in major human diseases. Embo J. 2021;40:e108863.
Xia H, Green DR, Zou W. Autophagy in tumour immunity and therapy. Nat Rev Cancer. 2021;21:281–97.
Suvac A, Ashton J, Bristow RG. Tumour hypoxia in driving genomic instability and tumour evolution. Nat Rev Cancer. 2025;25:167–88.
Qin W, Duan Y, Hu Z, Hou Y, Wen T, Ouyang Y, Wang Z, Sun X, Chen X, Wang KL, et al. PCK1 inhibits cGAS-STING activation by consumption of GTP to promote tumor immune evasion. J Exp Med. 2025;222:e20240902.
Mazure NM, Pouysségur J. Hypoxia-induced autophagy: cell death or cell survival? Curr Opin Cell Biol. 2010;22:177–80.
Vasquez Ayala A, Hsu CY, Oles RE, Matsuo K, Loomis LR, Buzun E, Carrillo Terrazas M, Gerner RR, Lu HH, Kim S, et al. Commensal bacteria promote type I interferon signaling to maintain immune tolerance in mice. J Exp Med. 2024;221:e20230063.
Porcari S, Ng SC, Zitvogel L, Sokol H, Weersma RK, Elinav E, Gasbarrini A, Cammarota G, Tilg H, Ianiro G. The Microbiome for clinicians. Cell. 2025;188:2836–44.
Silva CAC, Fidelle M, Almonte AA, Derosa L, Zitvogel L. Gut Microbiota-Related biomarkers in Immuno-Oncology. Annu Rev Pharmacol Toxicol. 2025;65:333–54.
Abraham S, Choi JG, Ortega NM, Zhang J, Shankar P, Swamy NM. Gene therapy with plasmids encoding IFN-β or IFN-α14 confers long-term resistance to HIV-1 in humanized mice. Oncotarget. 2016;7:78412–20.
Barnes SA, Audsley KM, Newnes HV, Fernandez S, de Jong E, Waithman J, Foley B. Type I interferon subtypes differentially activate the anti-leukaemic function of natural killer cells. Front Immunol. 2022;13:1050718.
Buzzai AC, Wagner T, Audsley KM, Newnes HV, Barrett LW, Barnes S, Wylie BC, Stone S, McDonnell A, Fear VS, et al. Diverse Anti-Tumor immune potential driven by individual IFNα subtypes. Front Immunol. 2020;11:542.
Newnes HV, Armitage JD, Buzzai AC, de Jong E, Audsley KM, Barnes SA, Srinivasan S, Serralha M, Fear VS, Guo BB, et al. Interleukin-4 modulates type I interferon to augment antitumor immunity. Sci Adv. 2025;11:eadt3618.