Barrierefreiheit    Kontakt MedUni Wien    Intranet    MedUni Wien - Shop    Universitätsbibliothek    Universitätsklinikum AKH Wien  
 
 
 
 
 


    Oncoimmunology. 2014 Dec 13. doi: 10.4161/21624011.2014.955691. pii: 955691. pmc: PMC4292729
    Consensus guidelines for the detection of immunogenic cell death.
    Kepp O1,  Senovilla L2,  Vitale I3,  Vacchelli E4,  Adjemian S5,  Agostinis P6,  Apetoh L7,  Aranda F8,  Barnaba V9,  Bloy N10,  Bracci L11,  Breckpot K12,  Brough D13,  Buqué A14,  Castro MG15,  Cirone M16,  Colombo MI17,  Cremer I18,  Demaria S19,  Dini L20,  Eliopoulos AG21,  Faggioni A22,  Formenti SC23,  Fučíková J24,  Gabriele L25,  Gaipl US26,  Galon J27,  Garg A28,  Ghiringhelli F29,  Giese NA30,  Guo ZS31,  Hemminki A32,  Herrmann M33,  Hodge JW34,  Holdenrieder S35,  Honeychurch J36,  Hu HM37,  Huang X38,  Illidge TM39,  Kono K40,  Korbelik M41,  Krysko DV42,  Loi S43,  Lowenstein PR44,  Lugli E45,  Ma Y46,  Madeo F47,  Manfredi AA48,  Martins I49,  Mavilio D50,  Menger L51,  Merendino N52,  Michaud M53,  Mignot G54,  Mossman KL55,  Multhoff G56,  Oehler R57,  Palombo F58,  Panaretakis T59,  Pol J60,  Proietti E61,  Ricci JE62,  Riganti C63,  Rovere-Querini P64,  Rubartelli A65,  Sistigu A66,  Smyth MJ67,  Sonnemann J68,  Spisek R69,  Stagg J70,  Sukkurwala AQ71,  Tartour E72,  Thorburn A73,  Thorne SH74,  Vandenabeele P75,  Velotti F76,  Workenhe ST77,  Yang H78,  Zong WX79,  Zitvogel L80,  Kroemer G81,  Galluzzi L82
    Author information
    Abstract

    Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named "immunogenic cell death" (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine.


    KEYWORDS: APC, antigen-presenting cell, ATF6, activating transcription factor 6, ATP release, BAK1, BCL2-antagonist/killer 1, BAX, BCL2-associated X protein, BCL2, B-cell CLL/lymphoma 2 protein, CALR, calreticulin, CTL, cytotoxic T lymphocyte, DAMP, damage-associated molecular pattern, DAPI, 4′,6-diamidino-2-phenylindole, DiOC6(3), 3,3′-dihexyloxacarbocyanine iodide, EIF2A, eukaryotic translation initiation factor 2A, ER, endoplasmic reticulum, FLT3LG, fms-related tyrosine kinase 3 ligand, G3BP1, GTPase activating protein (SH3 domain) binding protein 1, GFP, green fluorescent protein, H2B, histone 2B, HMGB1, HMGB1, high mobility group box 1, HSP, heat shock protein, HSV-1, herpes simplex virus type I, ICD, immunogenic cell death, IFN, interferon, IL, interleukin, MOMP, mitochondrial outer membrane permeabilization, PDIA3, protein disulfide isomerase family A, PI, propidium iodide, RFP, red fluorescent protein, TLR, Toll-like receptor, XBP1, X-box binding protein 1, autophagy, calreticulin, endoplasmic reticulum stress, immunotherapy, member 3, Δψm, mitochondrial transmembrane potential

    Publikations ID: 25941621
    Quelle: öffnen
     
    Drucken
     
    ccc_logo_en.gif
    ccc_logo_en.gif
    ccc_logo_en.gif

    Schnellinfo

     
     

    Featured

     
     
     
     
     
     
     
     
     
     
     
     
     
    © MedUni Wien |
     Impressum | Nutzungsbedingungen | Kontakt