6533b82bfe1ef96bd128e353

RESEARCH PRODUCT

Consensus guidelines for the detection of immunogenic cell death

O. KeppL. SenovillaI. VitaleE. VacchelliS. AdjemianP. AgostinisL. ApetohF. ArandaV. BarnabaN. BloyL. BracciK. BreckpotD. BroughA. BuquéMg CastroM. CironeMi ColomboI. CremerS. DemariaL. DiniA. EliopoulosA. FaggioniSc FormentiJ. Fu??íkováL. GabrieleUs GaiplJ. GalonA. GargF. GhiringhelliNa GieseZs GuoA. HemminkiM. HerrmannJw HodgeS. HoldenriederJ. HoneychurchHu HmX. HuangTm IllidgeK. KonoM. KorbelikDv KryskoS. LoiPr LowensteinE. LugliY. MaF. MadeoAa ManfrediI. MartinsP. MatzingerD. MavilioL. MengerN. MerendinoM. MichaudG. MignotKl MossmanG. MulthoffR. OehlerF. PalomboT. PanaretakisJ. PolE. ProiettiJe RicciChiara RigantiP. Rovere QueriniA. RubartelliA. SistiguMj SmythJ. SonnemannR. SpisekJ. StaggAq SukkurwalaE. TartourA. ThorburnSh ThorneP. VandenabeeleF. VelottiSr WorkenheH. YangWx ZongL. ZitvogelG. KroemerL. Galluzzi

subject

HSV-1 herpes simplex virus type IΔψm mitochondrial transmembrane potentialmedicine.medical_treatmentDAMP damage-associated molecular patterndetectionFLT3LG fms-related tyrosine kinase 3 ligandReviewmember 3calreticulinEukaryotic translation initiation factor 2ARFP red fluorescent protein0302 clinical medicineMOMP mitochondrial outer membrane permeabilizationImmunology and AllergyGFP green fluorescent proteinHMGB10303 health scienceseducation.field_of_studyToll-like receptorBAK1 BCL2-antagonist/killer 1H2B histone 2Bendoplasmic reticulum stre3. Good healthBAX BCL2-associated X proteinXBP1 X-box binding protein 1cell deathOncologyPDIA3 protein disulfide isomerase family A030220 oncology & carcinogenesisendoplasmic reticulum stressImmunogenic cell deathHSP heat shock proteinimmunotherapyTLR Toll-like receptorautophagyATF6 activating transcription factor 6ImmunologyICD immunogenic cell deathEIF2A eukaryotic translation initiation factor 2AGuidelinesBiologyBCL2 B-cell CLL/lymphoma 2 proteinER endoplasmic reticulumPI propidium iodideATP release03 medical and health sciencesImmune systemimmunogenicmedicineIFN interferonAntigen-presenting celleducation030304 developmental biologyCALR calreticulinDamage-associated molecular patternImmunotherapyCTL cytotoxic T lymphocyteHMGB1 high mobility group box 1IL interleukinG3BP1 GTPase activating protein (SH3 domain) binding protein 1APC antigen-presenting cellCancer cellImmunologyDiOC6(3) 33′-dihexyloxacarbocyanine iodideDAPI 4′6-diamidino-2-phenylindole

description

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. peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=koni20 ispartof: OncoImmunology vol:3 issue:9 pages:12472-124508 ispartof: location:United States status: published

https://doi.org/10.4161/21624011.2014.955691