2021, Número 3
Siguiente >>
Biotecnol Apl 2021; 38 (3)
Mecanismos moleculares de la Muerte Celular Inmunogénica: Una perspectiva desde los patrones moleculares asociados a daño y el estrés del retículo endoplasmático
de León-Esperón LM, Llorente AF, Díaz NO, Soto FC, Lanio ME, Álvarez C
Idioma: Ingles.
Referencias bibliográficas: 114
Paginas: 3102-3108
Archivo PDF: 572.13 Kb.
RESUMEN
Los regímenes terapéuticos que incrementan el potencial inmunogénico de las células tumorales para superar su fenotipo inmunoevasivo han alcanzado una gran relevancia en los últimos años. En este contexto, la inducción de la Muerte Celular Inmunogénica (ICD) emerge como una novedosa y promisoria estrategia para la terapia efectiva contra el cáncer. La ICD se caracteriza por la emisión de Patrones Moleculares Asociados al Daño (DAMPs) que actúan como señales de peligro en una configuración espaciotemporal precisa. Los DAMPs más significativamente involucrados en la percepción de la muerte celular como inmunogénica incluyen: la calreticulina expuesta en la superficie celular, el ATP extracelular, la proteína extracelular de alta movilidad del grupo caja 1 (HMGB1), los IFN de tipo I, los ácidos nucleicos extracelulares derivados de células moribundas y la anexina A1 extracelular (ANX A1). Estas señales de peligro asociadas a la ICD actúan sobre receptores expresados por las células del sistema inmune innato y como resultado ocurre la estimulación de la presentación de los antígenos tumorales a las células T. Esto genera una respuesta inmune adaptativa específica contra el tumor que puede controlar el crecimiento tumoral, e incluso, erradicar las células tumorales residuales. La ICD depende de la inducción concomitante de especies reactivas de oxígeno (ROS) y del estrés del retículo endoplasmático (ER). Las evidencias más recientes sitúan a la activación de la Respuesta a Proteínas No plegadas (UPR) y particularmente a la rama mediada por la proteína quinasa R similar a la quinasa del retículo endoplásmico (PERK) en el centro de muchos de los escenarios en los que se produce la ICD. Aquí ofrecemos una visión general de la comprensión actual de los mecanismos moleculares básicos que subyacen en la ICD. En esta revisión, nos centramos en la función crucial de los DAMPs y en la importancia del estrés del RE y de las ROS en la regulación de la inmunogenicidad de las células tumorales moribundas.
REFERENCIAS (EN ESTE ARTÍCULO)
Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol. 1994;12:991-1045.
Matzinger P. The danger model: a renewed sense of self. Science. 2002;296:301-5.
Casares N, Pequignot MO, TesniereA, Ghiringhelli F, Roux S, Chaput N, et al.Caspase-dependent immunogenicity ofdoxorubicin induced tumor cell death. JExp Med. 2005;202:1691-701.
Demaria S, Santori F, Ng B, Liebes L,Formenti SC, Vukmanovic S. Select formsof tumor cell apoptosis induce dendritic cellmaturation. J Leukoc Biol. 2005;77:361-8
Obeid M, Tesniere A, Ghiringhelli F,Fimia GM, Apetoh L, Perfettini JL, et al.Calreticulin exposure dictates the immunogenicityof cancer cell death. Nat Med.2007;13:54-61.
Galluzzi L, Vitale I, Aaronson S, AbramsJ, Adam D, Agostinis P, et al. Molecularmechanisms of cell death: recommendationsof the Nomenclature Committeeon Cell Death 2018. Cell Death Differ.2018;25:486-541.
Kroemer G, Galluzzi L, Kepp O, ZitvogelL. Immunogenic cell death in cancertherapy. Annu Rev Immunol. 2013;31:51-72.
Galluzzi L, Buqué A, Kepp O, ZitvogelL, Kroemer G. Immunogenic cell deathin cancer and infectious disease. Nat RevImmunol. 2017;17:97-111.
Tesniere A, Schlemmer F, Boige V, KeppO, Martins I, Ghiringhelli F, et al. Immunogenicdeath of colon cancer cells treatedwith oxaliplatin. Oncogene. 2009;29:482-91.
Martins I, Kepp O, Schlemmer F,Adjemian S, Tailler M, Shen S, et al.Restoration of the immunogenicity ofcisplatin-induced cancer cell death byendoplasmic reticulum stress. Oncogene.2011;30:1147-58.
Fucikova J, Moserova I, Truxova I,Hermanova I, Vancurova I, Partlova S,et al. High hydrostatic pressure inducesimmunogenic cell death in human tumorcells. Int J Cancer. 2014;135:1165-77.
Garg AD, Krysko DV, VandenabeeleP, Agostinis P. Hypericin-based photodynamictherapy induces surface exposure ofdamage-associated molecular patterns likeHSP70 and calreticulin. Cancer ImmunolImmunother. 2012;61:215-21.
Nuccitelli R, McDaniel A, Anand S, ChaJ, Mallon Z, Berridge JC, et al. Nano-PulseStimulation is a physical modality that cantrigger immunogenic tumor cell death. JImmunother Cancer. 2017;5:32.
Aaes TL, Kaczmarek A, Delvaeye T, DeCraene B, De Koker S, Heyndrickx L, et al.Vaccination with Necroptotic cancer cellsinduces efficient anti- tumor immunity. CellRep. 2016;15:274-87.
Yang H, Ma Y, Chen G, Zhou H,Yamazaki T, Klein C, et al. Contributionof RIP3 and MLKL to immunogenic celldeath signaling in cancer chemotherapy.Oncoimmunology. 2016;5:e1149673.
Garg AD, Nowis D, Golab J, VandenabeeleP, Krysko DV. Immunogenic celldeath, DAMPs and anticancer therapeutics:an emerging amalgamation. BiochimBiophys Acta. 2010;1805:53-71.
Krysko DV, Garget AD, Kaczmarek A,Krysko O, Agostinis P, Vandenabeele P, etal. Immunogenic cell death and DAMPs incancer therapy. Nat Rev Cancer. 2012; 12:860–875.
Panaretakis T, Kepp O, BrockmeierU, Tesniere A, Bjorklund AC, ChapmanDC, et al. Mechanisms of pre-apoptoticcalreticulin exposure in immunogenic celldeath. EMBO J. 2009;28:578-90.
Elliott M, Chekeni F, Trampont P,Lazarowski E, Kadl A, Walk SF, et al.Nucleotides released by apoptotic cells actas a find-me signal to promote phagocyticclearance. Nature. 2009;461:282-6.
Ghiringhelli F, Apetoh L, Tesniere A,Aymeric L, Ma Y, Ortiz C, et al. Activationof the NLRP3 inflammasome in dendriticcells induces IL-1β-dependent adaptiveimmunity against tumors. Nat Med.2009;15:1170-8.
Scaffidi P, Misteli T, Bianchi ME. Releaseof chromatin protein HMGB1 by necroticcells triggers inflammation. Nature.2002;418:191-5.
Apetoh L, Ghiringhelli F, Tesniere A,Obeid M, Ortiz C, Criollo A, et al. Tolllikereceptor 4-dependent contributionof the immune system to anticancer chemotherapyand radiotherapy. Nat Med.2007;13:1050-9.
Sistigu A, Yamazaki T, Vacchelli E,Chaba K, Enot D, Adam J, et al. Cancercell-autonomous contribution of typeI interferon signaling to the efficacy ofchemotherapy. Nat Med. 2014;20:1301-9.
Vanpouille-Box C, Alard A, AryankalayilMJ, Sarfraz Y, Diamond J, SchneiderR, et al. DNA exonuclease Trex1 regulatesradiotherapy-induced tumour immunogenicity.Nat Commun. 2017;8:15618.
Chiba S, Baghdadi M, Akiba H, YoshiyamaH, Kinoshita I, Dosaka-Akita H, etal. Tumor-infiltrating DCs suppress nucleicacid-mediated innate immune responsesthrough interactions between the receptorTIM-3 and the alarmin HMGB1. Nat Immunol.2012;13(9):832-42.
Garg AD, Vandenberk L, Fang S, FascheT, Van Eygen S, Maes J, et al. Pathogenresponse-like recruitment and activationof neutrophils by sterile immunogenicdying cells drives neutrophil-mediatedresidual cell killing. Cell Death Differ.2017;24:832-43.
Vacchelli E, Ma Y, Baracco EE, SistiguA, Enot DP, Pietrocola F, et al. Chemotherapy-Induced antitumor immunity requiresformyl peptide receptor 1. Science.2015;350:972-8.
Green DR, Ferguson T, Zitvogel L, KroemerG. Immunogenic and tolerogenic celldeath. Nat Rev Immunol. 2009;9:353-63.
Grivennikov S, Greten F, Karin M. Immunity,inflammation, and cancer. Cell.2010;140:883-99.
Garg AD, Vandenberk L, Koks C,Verschuere T, Boon L, Van Gool SW, etal. Dendritic cell vaccines based on immunogeniccell death elicit danger signalsand T cell- driven rejection of high- gradeglioma. Sci Transl Med. 2016;8:328ra327.
Kepp O, Senovilla L, Vitale I, VacchelliE, Adjemian S, Agostinis P, et al.Consensus guidelines for the detection ofimmunogenic cell death. Oncoimmunology.2014;3:e955691.
Sukkurwala AQ, Adjemian S, SenovillaL, Michaud M, Spaggiari S, Vacchelli E, etal. Screening of novel immunogenic celldeath inducers within the NCI mechanisticdiversity set. Oncoimmunology.2014;3:e28473.
Dunn G, Bruce A, Ikeda H, Old L,Schreiber RD. Cancer immunoediting: fromimmunosurveillance to tumor escape. NatImmunol. 2002;3:991-8.
Vesely M, Kershaw M, Schreiber R,Smyth M. Natural innate and adaptiveimmunity to cancer. Annu Rev Immunol.2011;29:235-71.
Zitvogel L, Tesniere A, Kroemer G.Cancer despite immunosurveillance: immunoselectionand immunosubversion.Nat Rev Immunol. 2006;6:715-27.
Hanahan D, Weinberg RA. Hallmarksof cancer: the next generation. Cell.2011;144:646e674.
Meije C, Swart G, Lepoole C, Das P,van den Oord JJ. Antigenic profiles ofindividual-matched pairs of primary andmelanoma metastases. Hum Pathol.2009;40:1399-407.
Gubin M, Artyomov M, Mardis E,Schreiber R. Tumor neoantigens: buildinga framework for personalized cancerimmunotherapy. J Clin Invest. 2015;125:3413-21.
van Kempen T, Wenink M, LeijtenE, Radstake T, Boes M. Perception ofself: distinguishing autoimmunity fromautoinflammation. Nat Rev Rheumatol.2015;11:483-92.
Chekeni FB, Elliott MR, SandilosJK, Walk SF, Kinchen JM, LazarowskiER, et al. Pannexin 1 channels mediate‘find-me’ signal release and membranepermeability during apoptosis. Nature.2010;467(7317):863-7.
Yamazaki T, Buqué A, Rybstein M,Chen J, Sato A, Galluzzi L. Methods toDetect Immunogenic Cell Death In Vivo.In: Thurin M, Cesano A, Marincola F (eds).Biomarkers for Immunotherapy of Cancer.Methods in Molecular Biology, vol 2055.Humana, New York, NY; 2020.
Gelebart P, Opas M, Michalak M.Calreticulin, a Ca2+-binding chaperone ofthe endoplasmic reticulum. Int J BiochemCell Biol. 2005;37:260-6.
Gardai SJ, McPhillips KA, Frasch SC,Janssen WJ, Starefeldt A, Murphy-UllrichJE, et al. Cell-surface calreticulin initiatesclearance of viable or apoptotic cellsthrough trans-activation of LRP on thephagocyte. Cell. 2005;123:321-3.
Pawaria S, Binder R. CD91-dependentprogramming of T-helper cell responsesfollowing heat shock protein immunization.Nat Commun. 2011;2:521.
Majeti R, Chao M, Alizadeh A, Pang W,Jaiswal S, Gibbs Jr KD, et al. CD47 is anadverse prognostic factor and therapeuticantibody target on human acute myeloidleukemia stem cells. Cell. 2009;138:286-99.
Suzuki S, Yokobori T, Tanaka N, SakaiM, Sano A, Inose T, et al. CD47 expressionregulated by the miR-133a tumorsuppressor is a novel prognostic markerin esophageal squamous cell carcinoma.Oncol Rep. 2012;28:465-72.
Barclay AN, van den Berg TK. The interactionbetween signal regulatory proteinalpha (SIRPalpha) and CD47: structure,function, and therapeutic target. Annu RevImmunol. 2014;32:25-50.
Chao MP, Jaiswal S, Weissman-TsukamotoR, Alizadeh A, Gentles AJ, VolkmerJ, et al. Calreticulin is the dominantpro-phagocytic signal on multiple humancancers and is counterbalanced by CD47.Sci Transl Med. 2010;2:63ra94.
Wemeau M, Kepp O, Tesniere A, PanaretakisT, Flament C, De Botton S, et al.Calreticulin exposure on malignant blastspredicts a cellular anticancer immuneresponse in patients with acute myeloidleukemia. Cell Death Dis. 2010;1:e104.
Selzner N, Selzner M, Graf R, UngethuemU, Fitz JG, Clavien PA. Water inducesautocrine stimulation of tumor cell killingthrough ATP release and P2 receptor binding.Cell Death Differ. 2004;11:172-80.
Martins I, Wang Y, Michaud M, Ma Y,Sukkurwala AQ, Shen S, et al. Molecularmechanisms of ATP secretion during immunogeniccell death. Cell Death Differ.2014;21:79-91.
Wang Y, Martins I, Ma Y, Kepp O, GalluzziL, Kroemer G. Autophagy-dependentATP release from dying cells via lysosomalexocytosis. Autophagy. 2013;9(10):1624-5.
Michaud M, Martins I, SukkurwalaA, Adjemianet S, Ma Y, Pellegatti P, et al.Autophagy-dependent anticancer immuneresponses induced by chemotherapeuticagents in mice. Science. 2011;334:1573-7.
Garg AD, Dudek AM, Agostinis P. Autophagy-dependent suppression of cancerimmunogenicity and effector mechanismsof innate and adaptive immunity. Oncoimmunology.2013;2:10.
Kepp O, Kroemer G. Autophagyinduction by thiostrepton for the improvementof anticancer therapy. Autophagy.2020;16:1166-7.
Antonioli L, Blandizzi C, Pacher P, HaskóG. Immunity, inflammation and cancer:a leading role for adenosine. Nat RevCancer. 2013;13:842-57.
Sun X, Wu Y, Gao W, Enjyoji K, CsizmadiaE, Müller CE, et al. CD39/ENTPD1expression by CD4+Foxp3+ regulatoryT cells promotes hepatic metastatic tumorgrowth in mice. Gastroenterology.2010;139:1030-40.
Zitvogel L, Kepp O, Galluzzi L, KroemerG. Inflammasomes in carcinogenesis andanticancer immune responses. Nat Immunol.2012;13:343-51.
Ma Y, Aymeric L, Locher C, MattarolloSR, Delahaye NF, Pereira P, et al. Contributionof IL-17-producing γδT cells to theefficacy of anticancer chemotherapy. J ExpMed. 2011;208:491-503.
Isaacs A, Lindenmann J. Virus interference.I. The interferon. Proc R Soc Lond BBiol Sci. 1957;147:258-67.
McNab F, Mayer-Barber K, Sher A,Wack A, O’garra A. Type I interferonsin infectious disease. Nat Rev Immunol.2015;15:87-103.
Mackenzie KJ, Carroll P, Martin CA,Murina O, Fluteau A, Simpson DJ, et al.cGAS surveillance of micronuclei linksgenome instability to innate immunity.Nature. 2017;548(7668):461-5.
Papewalis C, Jacobs B, Wuttke M,Ullrich E, Baehring T, Fenk R, et al. IFN-αskews monocytes into CD56+-expressingdendritic cells with potent functionalactivities in vitro and in vivo. J Immunol.2008;180:1462-70.
Crouse J, Bedenikovic G, Wiesel M,Ibberson M, Xenarios I, Von Laer D, et al.Type I interferons protect T cells againstNK cell attack mediated by the activatingreceptor NCR1. Immunity. 2014;40(6):961-73.
Xu H, Grusdat M, Pandyra A, Polz R,Huang J, Sharma P, et al. Type I interferonprotects antiviral CD8+ T cells from NK cellcytotoxicity. Immunity. 2014;40(6):949-60.
Novikov A, Cardone M, Thompson R,Shenderov K, Kirschman KD, Mayer-BarberKD, et al. Mycobacterium tuberculosis triggershost type I IFN signaling to regulate IL-1beta production in human macrophages.J Immunol. 2011;187:2540-7.
Deng L, Liang H, Xu M, Yang X, BurnetteB, Arina A, et al. STING-dependent cytosolicDNA sensing promotes radiation-inducedtype I interferon-dependent antitumor immunityin immunogenic tumors. Immunity.2014;41:843-52.
Woo SR, Fuertes MB, Corrales L, SprangerS, Furdyna MJ, Leung MYK et al. STINGdependentcytosolic DNA sensing mediatesinnate immune recognition of immunogenictumors. Immunity. 2014;41:830-42.
Bidwell B, Slaney C, Withana N, ForsterS, Cao Y, Loi S, et al. Silencing of Irf7 pathwaysin breast cancer cells promotes bonemetastasis through immune escape. NatMed. 2012;18:1224-31.
Perretti M, D’Acquisto F. Annexin A1 andglucocorticoids as effectors of the resolutionof inflammation. Nat Rev Immunol. 2009;9:62-70.
Goodwin GH, Johns EW. Isolation andcharacterisation of two calf-thymus chromatinnon-histone proteins with high contents ofacidic and basic amino acids. Eur J Biochem.1973;40(1):215-9.
Bustin M. Regulation of DNA-dependentactivities by the functional motifs of the highmobility-group chromosomal proteins. MolCell Biol. 1999;19(8):5237-46.
Bonaldi T, Talamo F, Scaffidi P, FerreraD, Porto A, Bachi A, et al. Monocytic cellshyperacetylate chromatin protein HMGB1to redirect it towards secretion. EMBO J.2003;22:5551-60.
Evankovich J, Cho S, Zhang R, CardinalJ, Dhupar R, Zhang L, et al. High mobilitygroup box 1 release from hepatocytes duringischemia and reperfusion injury is mediatedby decreased histone deacetylase activity. JBiol Chem. 2010;285(51):39888-97.
Jorgensen I, Miao EA. Pyroptotic cell deathdefends against intracellular pathogens. ImmunolRev. 2015;265(1):130-42.
Lu A, Magupalli VG, Ruan J, Yin Q,Atianand MK, Vos MR, et al. Unified PolymerizationMechanism for the Assembly of ASC-Dependent Inflammasomes. Cell.2014;156:1193-1206.
Liu X, Lieberman J. Knocking ’em Dead:Pore-forming proteins in immune defense.Annu Rev Immunol. 2020;38:455-85.
Van Opdenbosch N, Lamkanfi M.Caspases in cell death, inflammation, anddisease. Immunity. 2019;50:1352-64.
Liu X, Zhang Z, Ruan J, Pan Y, MagupalliVG, Wu H, et al. Inflammasome-activatedgasdermin D causes pyroptosis by formingmembrane pores. Nature. 2016;535:153-8.
de Vasconcelos NM, Van OpdenboschN, Van Gorp H, Parthoens E, Lamkanfi M.Single-cell analysis of pyroptosis dynamicsreveals conserved GSDMD-mediated subcellularevents that precede plasma membranerupture. Cell Death Differ. 2018;26:146-61.
Chen G, Ward MF, Sama AE, Wang H.Extracellular HMGB1 as a proinflammatorycytokine. J Interferon Cytokine Res.2004;24:329-33
Park JS, Gamboni-Robertson F, He Q,Svetkauskaiteet D, Kim JY, Strassheim D,et al. High mobility group BOX 1 proteininteracts with multiple Toll-like receptors. AmJ Physiol Cell Physiol. 2006;290:C917-24.
Andersson U, Wang H, Palmblad K,Aveberger AC, Bloom O, Erlandsson-HarrisH, et al. High mobility group 1 protein (Hmg-1) stimulates proinflammatory cytokinesynthesis in human monocytes. J Exp Med.2000;192(4):565-70.
Tang D, Billiar TR, Lotze MT. A JanusTale of Two Active High Mobility GroupBox 1 (HMGB1) redox states. Mol Med.2012;18:1360-2.
Venereau E, Casalgrandi M, SchiraldiM, Antoine DJ, Cattaneo A, De MarchisF, et al. Mutually exclusive redox forms ofHMGB1 promote cell recruitment or proinflammatorycytokine release. J Exp Med.2012;209(9):1519-28.
Yang H, Lundbäck P, Ottosson L, Erlandsson-Harriset H, Venereau E, Bianchi ME, etal. Redox modification of cysteine residuesregulates the cytokine activity of HighMobility Group Box-1 (HMGB1). Mol Med.2012;18:250-9.
Rufo N, Garg AD, Agostinis P. The UnfoldedProtein Response in Immunogenic CellDeath and Cancer Immunotherapy. Trendsin Cancer. 2017;3(9):643-58.
Garg AD, Krysko DV, Verfaillie T, KaczmarekA, Ferreira GB, Marysael T, et al.A novel pathway combining calreticulinexposure and ATP secretion in immunogeniccancer cell death. EMBO J. 2012;31:1062-79.
Garg AD, Martin S, Golab J, Agostinis P.Danger signalling during cancer cell death:origins, plasticity and regulation. Cell DeathDiffer. 2014;21:26-38.
Obeng EA, Carlson LM, Gutman DM,Harrington WJ, Lee KP, Boise LH. Proteasomeinhibitors induce a terminal unfolded proteinresponse in multiple myeloma cells. Blood.2006;107:4907-17.
Almanza A, Carlesso A, Chintha C,Creedican S, Doultsinos D, Leuzzi B, et al.Endoplasmic reticulum stress signalling – frombasic mechanisms to clinical applications.FEBS J. 2019;286:241-78.
Shen K, Johnson DW, Vesey DA, McGuckinMA, Gobe GC. Role of the unfolded proteinresponse in determining the fate of tumor cellsand the promise of multi-targeted therapies.Cell Stress Chaperones. 2018;23:317-34.
Michaud M, Sukkurwala AQ, Di Sano F,Zitvogel L, Kepp O, Kroemer G. Synthetic inductionof immunogenic cell death by geneticstimulation of endoplasmic reticulum stress.Oncoimmunology. 2014;3:28276.
Garg AD, Galluzzi L, Apetoh L, Baert T,Birge RB, Bravo-San Pedro JM, et al. Molecularand translational classifications of DAMPsin immunogenic cell death. Front Immunol.2015;6:588.
van Vliet AR, Garg AD, Agostinis P. Coordinationof stress, Ca2+ and immunogenic signalingpathways by PERK at the endoplasmicreticulum. Biol Chem. 2016;397(7):649-56.
Kepp O, Menger L, Vacchelli E, Locher C,Adjemian S, Yamazaki T, et al. Crosstalk betweenER stress and immunogenic cell death.Cytokine Growth Factor Rev. 2013;24:311-8.
Serrano-del Valle A, Anel A, Naval J,Marzo I. Immunogenic cell death and immunotherapyof multiple myeloma. Front CellDev Biol. 2019;7:50.
van Vliet AR, Giordano F, Gerlo S, SeguraI, Van Eygen S, Molenberghs G, et al. The ERstress sensor PERK coordinates ER-plasmamembrane contact site formation throughinteraction with Filamin-A and F-actin remodeling.Mol Cell. 2017;65:1-15.
Varnai P, Hunyady L, Balla T. STIM andOrai: the long-awaited constituents of storeoperatedcalcium entry. Trends Pharmacol Sci.2009;30:118-28.
Luik R, Wu M, Buchanan J, Lewis R. Theelementary unit of store-operated Ca2+ entry:local activation of CRAC channels by STIM1at ER-plasma membrane junctions. J Cell Biol.2006;174:815-25.
Wu M, Buchanan J, Luik R, Lewis R. Ca2+store depletion causes STIM1 to accumulate inER regions closely associated with the plasmamembrane. J Cell Biol. 2006;174:803-13.
Orci L, Ravazzola M, Le Coadic M,Shen W, Demaurex N, Cosson P. From theCover: STIM1-induced precortical andcortical subdomains of the endoplasmic reticulum.Proc Natl Acad Sci USA. 2009;106:19358-62.
Porat-Shliom N, Milberg O, MasedunskasA, Weigert R. Multiple roles for the actincytoskeleton during regulated exocytosis. CellMol Life Sci. 2013;70:2099-121.
Tufi R, Panaretakis T, Bianchi K, CriolloA, Fazi B, Di Sano F, et al. Reduction of endoplasmicreticulum Ca2+ levels favors plasmamembrane surface exposure of calreticulin.Cell Death Differ. 2008;15:274-82.
Menger L, Vacchelli E, Adjemian S,Martins I, Ma Y, Shen S, et al. Cardiac glycosidesexert anticancer effects by inducingimmunogenic cell death. Sci Transl Med.2012;4(143):ra99.
Peters L, Raghavan M. Endoplasmicreticulum calcium depletion impacts chaperonesecretion, innate immunity, andphagocytic uptake of cells. J Immunol.2011;187:919-31.
Cekic C, Linden J. Purinergic regulationof the immune system. Nat Rev Immunol.2016;16:177-92.
Hangai S, Ao T, Kimura Y, Matsuki K,Kawamura T, Negishi H, et al. Pge2 inducedin and released by dying cells functions asan inhibitory DAMP. Proc Natl Acad Sci USA.2016;113:3844-9.
Green DR, Galluzzi L, Kroemer G.Metabolic control of cell death. Science.2014;345:1250256
Verfaillie T, Rubio N, Garg AD, BultynckG, Rizzuto R, Decuypere JP, et al. PERK isrequired at the ER-mitochondrial contactsites to convey apoptosis after ROS-based ERstress. Cell Death Differ. 2012;19:1880-91.
Deng H, Zhou Z, Yang W, Lin L, WangS, Niu G et al. Endoplasmic reticulum targetingto amplify immunogenic cell deathfor cancer immunotherapy. Nano Lett.2020;20:1928-33.
Li W, Yang J, Luo L, Jiang M, Qin B, YinH, et al. Targeting photodynamic and photothermaltherapy to the endoplasmic reticulumenhances immunogenic cancer cell death.Nat Commun. 2019;10:3349.
Pol J, Vacchelli E, Aranda F, Castoldi F,Eggermont A, Cremer I, et al. Trial watch:immunogenic cell death inducers for anticancerchemotherapy. Oncoimmunology.2015;4:e1008866.
Vanmeerbeek I, Sprooten J, De RuysscherD, Tejpar S, Vandenberghe P, Fucikova J,et al. Trial watch: chemotherapy-induced immunogeniccell death in immuno-oncology.Oncoimmunology. 2020;9(1):1703449.