Insights into Immunogenic Cell Death: Comparison
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Please note this is a comparison between Version 1 by Marianna Christodoulou and Version 2 by Jessie Wu.

Immunogenic cell death (ICD) is a type of regulated cell death (RCD), increasingly studied in recent years, due to its therapeutic implication in several diseases associated with immune system dysfunction. The new and increasingly studied concept of immunogenic cell death (ICD) revealed a previously unknown perspective of the various regulated cell death (RCD) modalities, elucidating their immunogenic properties and rendering obsolete the notion that immune stimulation is solely the outcome of necrosis. A distinct characteristic of ICD is the release of danger-associated molecular patterns (DAMPs) by dying and/or dead cells. These are evolutionary conserved stress signals, recognized primarily by innate immune system receptors. The immunogenicity of DAMPs characterizes ICD, rendering them potential prognostic, diagnostic clinical tools and/or possible therapeutic targets.

  • ICD
  • DAMPs
  • apoptosis
  • necroptosis
  • pyroptosis
  • parthanatos
  • ferroptosis

1. Introduction

Immunogenic cell death (ICD) defines various RCD processes which, upon stimulation by endogenous antigenic components from dying or dead cells, lead to an enhanced T cell-dependent immune response [1][2][3]. Immunogenicity derives from the synergy of these antigens with DAMPs (also termed alarmins), which act as adjuvants when secreted/excreted in the microenvironment of dying cells [1][2][4]. ICD is also characterized by the production of high levels of reactive oxygen species (ROS) and is highly related to endoplasmic reticulum (ER) stress, often resulting in an unfolded protein response (UPR) [5].
For years, the common conception regarding the way by which cells die has been fallaciously limited to the dipole apoptosis/necrosis [4][6]. The apoptotic process, historically considered as solely representing RCD, is characterized by programmed morphological changes occurring in the apoptotic cell, including the initial DNA fragmentation and the subsequent formation of apoptotic bodies, i.e., membrane vesicles enwrapping intracellular material [7][8]. These changes often promote the recognition and engulfment of the shrunken apoptotic cell or smaller membranous portions thereof by phagocytes, in a non-immunologically-mediated manner [6][8][9]. Thus, apoptotic cell death has been considered as immunologically “silent” and, subsequently, immunologically tolerated [3][10][11][12]. On the other hand, necrosis and, later on, necroptosis, have been strongly associated with inflammation [3][6][8][13][14]. Nonetheless, scientific data clarified this long-held misconception and rendered some RCD types as potential inducers of adaptive immune responses [6][15]. Galluzzi et al. [16] and Kroemer et al. [17] elegantly described that the immunological outcome of RCD, i.e., whether immunogenic or tolerogenic, depends on the presence of antigens (antigenicity), on potent and immunostimulatory adjuvant-like signals (adjuvanticity) and on the “shaping” of an immune-permissive microenvironment. In the therapeutic management of tumors, treatment with low-dose chemotherapy (e.g., anthracyclins) or low-dose ionizing radiation (IR; e.g., γ-rays) induces ICD. The latter is associated with tumor-antigen shedding and translocation or release of DAMPs (e.g., calreticulin (CRT), high-mobility group box 1 protein (HMGB1), adenosine triphosphate (ATP)) by dying cells, which bind to innate immune receptors on antigen-presenting cells (APCs); the concomitantly released type I interferons (IFNs) and interleukin (IL)-1β modulate the microenvironment to support APC maturation and trafficking to the draining lymph nodes, where they dictate T cell activation and proliferation; tumor-reactive T cells further traffic to the tumor, rapidly eliminate cancer cells and ultimately, culminate in tumor antigen-specific immunological memory (Figure 1). On the contrary, apoptotic non-inflammatory RCD induced for example by high-dose chemotherapy or radiation, causes blebbing of the tumor-cell membrane, loss of tumor-antigen(s) and of DAMP secretion/excretion, impedes APC activation and secretion of pro-inflammatory cytokines, and consequently, inhibits the activities of effector T cells, finally leading to immunosuppression [18][19].
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Figure 1. Differences in adaptive immune responses following induction of ICD and non-immunogenic RCD. (A) In ICD, type I ICD inducers trigger indirect ER stress; type II ICD inducers trigger direct ER stress. The dying cancer cell releases tumor antigens and DAMPs (e.g., HMGB1, ATP, proTα(100–109)), while “eat-me” signals (e.g., CRT) are exposed on the cell surface (A1). Maturation of APCs increases cancer antigen uptake and MHC class II and I are overexpressed (A2). Mature APCs traffic to the draining lymph node, produce Th1-polarizing cytokines and chemokines, and activate helper T (Th1) and cytotoxic T cells (CTLs) (A3). CTLs traffic to the tumor and, via the secretory (perforin) or the non-secretory (Fas-FaL) pathways, kill cancer cells (A4). The de novo released tumor antigens and DAMPs act as feedback signals and refuel the ICD cycle (arrow). (B) In non-immunogenic RCD, the dying cancer cell does not release tumor antigens and DAMPs (B1), APCs are not activated (B2), helper and cytotoxic T cell responses are not stimulated (B3), and cancer cells remain viable (B4).
Unlike the accidental/necrotic cell death (ACD) caused by various physical, chemical, and mechanical cell injuries, RCD is elegantly controlled by a plethora of molecular signaling pathways. Well-characterized RCD modalities reported to stimulate immunogenic properties through the release of DAMPs are shown in Figure 2.
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Figure 2. An overview of ICD mechanisms and key regulatory molecules. The main ICD modalities shown are apoptosis and necroptosis (A), ferroptosis (B), parthanatos (C), and pyroptosis (D). Arrows indicate the pathway flow and the relative regulatory molecules. AIF, apoptosis-inducing factor; ASC, apoptosis-associated speck-like protein containing a CARD; BAK, Bcl-2 homologous antagonist killer; BAX, Bcl-2-like protein 4; FADD, FAS-associated death domain protein; GPX4, glutathione peroxidase 4; MLKL, mixed lineage kinase domain-like pseudokinase; NLRs, NOD-like receptors; PARP1, poly(ADP-ribose) polymerase-1; RIPK, receptor-interacting protein kinase; ROS, reactive oxygen species; TLR, Toll-like receptor; and TRADD, tumor necrosis factor receptor type 1-associated death domain protein.

2. Apoptosis

Apoptosis is the most extensively studied type of RCD. An apoptotic cell undergoes a variety of rigorously programmed processes that affect its morphology, including the condensation and fragmentation of chromatin, the rupture of the nucleus, and a decrease of cellular volume and blebbing, which, finally, result in the formation of apoptotic bodies. Apoptotic bodies contain intracellular material and organelles and are eventually cleared by non-professional (e.g., macrophages) and professional (e.g., dendritic cells (DCs)) phagocytes, via a process known as efferocytosis [2][8]. Based on the stimulus that initiates the apoptotic cascade, apoptosis may be mediated by two distinct pathways, the extrinsic and the intrinsic [2][20][21].
The extrinsic or receptor-mediated pathway is initiated by the stimulation of death receptors, belonging to the tumor necrosis factor (TNF) family, such as CD95 (APO-1/Fas) or TNF-related apoptosis-inducing ligand (TRAIL), that activate caspase-8, the primary initiator of the caspase cascade. Caspase-8 is responsible for the direct cleavage of downstream effector caspases, such as caspase-3 [2][7][21][22].
The intrinsic or mitochondrial pathway is initiated by stress-induced signals, followed by the release and accumulation of apoptogenic, mitochondria-derived factors in the cytoplasm, such as cytochrome c, apoptosis-inducing factor (AIF), the second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI (Smac/DIABLO), the serine protease high-temperature requirement A2 (HtrA2/Omi), and endonuclease G. Accumulation of cytochrome c in the cytoplasm triggers the formation of the cytochrome c/apoptotic protease-activating factor 1 (Apaf-1) apoptosome complex, which recruits and activates pro-caspase-9, subsequently resulting in the activation of caspase-3. Smac/DIABLO and HtrA2/Omi interact with and antagonize the inhibitor-of-apoptosis proteins (IAPs), whereas AIF and endonuclease G translocate to the nucleus, thus promoting DNA condensation [2][7][20][21][23].
Numerous studies have shown that apoptosis mediated by either the extrinsic or the intrinsic pathway can be immunogenic [24]. Albert et al. first observed that human DCs can efficiently present antigens derived from apoptotic monocytes previously infected with influenza A virus and stimulate major histocompatibility complex (MHC) class I-restricted CD8+ cytotoxic T lymphocytes (CTLs) [25]. It was further shown that protein cleavage, generated by activated caspases during apoptosis, facilitates antigen processing and cross-presentation by DCs [26][27]. At the same time, the release of DAMPs by apoptotic cells triggers immune responses. Specifically, tumor cells treated with doxorubicin (DX) and other anthracyclines, oxaliplatin (OXP) or IR, elicit anticancer immune responses in vivo and thus, grant protection to mice against tumor growth [15][27][28]. This procedure involves the release of various DAMPs by apoptotic cells, including CRT, members of the heat shock protein (HSP) family, such as HSP70 and HSP90, HMGB1 and ATP. These molecules are essential prerequisites for characterizing an RCD case as immunogenic [27]. The aforementioned data suggest that apoptotic cells may be immunogenic, whereas necrotic cells induce excessive inflammation, due to the massive release of DAMPs, but are incapable of eliciting potent CD8+ T cell responses [24][29].

3. Necroptosis

Necroptosis is a type of RCD, morphologically resembling necrosis. It is triggered by the stimulation of TNF receptors, such as TNF receptor 1 (TNFR1) and Fas [2][30], or pattern recognition receptors (PRRs), such as DNA-dependent activator of interferon-regulatory factors (DAI) and Toll-like receptors (TLRs) 3 and 4 [2][31]. Via signal transduction, the receptor-interacting protein kinase (RIPK) 1 is activated and RIPK3 is consequently recruited. RIPK3 further activates the mixed lineage kinase domain-like pseudokinase (MLKL), which promotes cell membrane breaching and cell death, with simultaneous spilling of intracellular content that contains pro-inflammatory cytokines and DAMPs [2]. The aforementioned DAMPs, together with the released cytokines and chemokines, render necroptotic cells immunogenic and thus, able to elicit CD8+ T cell-mediated responses, including potent anticancer responses [4][3], since necroptosis bypasses tumor cell resistance to apoptosis.

4. Pyroptosis

Pyroptosis is an RCD modality initiated by intracellular and extracellular homeostatic perturbations, associated with the innate arm of immunity [7]. Specifically, it is triggered in response to pathogenic infections, e.g., with Salmonella spp. [32]. Similarly to necroptosis, pyroptotic cells present a necrotic morphology, characterized by plasma membrane rupture that results in the release of their cellular content [7][32]. In general, it occurs in phagocytes, such as macrophages, DCs and neutrophils, although it has been observed in other cell types as well. The mechanism of pyroptosis is strongly linked to the enzymatic activity of caspases, especially of caspase-1, and its activation associates with inflammasomes—cytosolic structures assembled by activated specific PRRs [33]. This activation results in the release of IL-1β, a pyrogenic cytokine that induces fever and recruits immune cells to the infected tissue, and IL-18, which conditionally promotes either T helper (Th) 1 or Th2 immune responses. Furthermore, as the pyroptotic process involves membrane breaching, it consequently leads to the release, among other intracellular components, of DAMPs, such as HMGB1, several S100 proteins, and IL-18α [32][33]. Strong evidence suggests that neutrophil pyroptosis may play a pivotal role in sepsis [34].

5. Ferroptosis

Ferroptosis also shares common morphological characteristics with necrosis and is triggered by cellular homeostatic disturbances, associated with impaired regulation of intracellular iron levels, leading to a lethal iron-dependent accumulation of lipid hydroperoxides [35][36]. This severe lipid peroxidation is associated with the release of immunostimulatory DAMPs, such as HMGB1, and cytokines, such as IL-1β and IL-18, by the ferroptotic cell, thus rendering the ferroptotic process immunogenic [37][38].

6. Parthanatos

Parthanatos is another form of RCD that features necrotic-like morphology. It is the result of severe/prolonged alkylating DNA damage and is driven by hyperactivation of a specific component of the DNA damage response. It is also involved in the pathogenesis of several conditions, such as ischemia-reperfusion injury, hypoxia, inflammation, myocardial infarction, glutamate excitotoxicity and Parkinson’s disease [7][39]. The key molecule implicated in the mechanism of parthanatos is poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear protein that plays an important role in DNA repair, genomic stability, and transcription [39][40]. In cells facing excessive DNA damage, overactivation of PARP-1 eventually drives cells to RCD, as a result of the depletion of cellular energy, the mitochondrial release of AIF, and the production of excess poly(ADP-ribose) (PAR) polymers [39]. Activation of PARP-1 induces the release of immunogenic alarmins, primarily of HMGB1.
Overall, based on this evidence, various RCD processes can likely be deemed as forms of ICD. Some additional death types include anoikis (an apoptotic RCD modality) [1][7][41][42], mitochondrial permeability transition (MPT)-driven necrosis [7], entotic cell death (entosis) [7][43], the neutrophil extracellular trap (NET) cell death or NETosis [7][43][44], lysosome-dependent cell death (LDCD) [7][43], autophagy-dependent cell death (ADCD) [7][43], autosis [7][43][45], alkaliptosis [43], and oxeiptosis [43], but their detailed analysis is beyond the scope of this resviearchw. Major types of ICD along with their morphological characteristics and immunologic profiles are briefly presented in Table 1, and regulatory molecules required for ICD induction and coordination of the process are comparatively shown in Figure 2.
Table 1. The classification and characteristics of various cell death modalities. Important regulators mediating each death type are listed in the last column.
Cell Death Modality Classification Morphological Characteristics Immunologic Profile Regulators
Necrosis ACD cell swelling; DNA fragmentation; membrane rupture; loss of cell organelles Tolerogenic/immunogenic None
Apoptosis RCD cell shrinkage/rounding; nuclear condensation/fragmentation; nuclear membrane rupture; membrane blebbing; apoptotic body formation Tolerogenic/immunogenic Death receptors, BAX, BAK, AIF, caspases 2, 3, 6, 7, 8, and 9
Necroptosis RCD cell/mitochondrial swelling; membrane rupture; chromatin condensation; loss of cell organelles Immunogenic TLRs, TCR, RIPK1, RIPK3, MLKL
Pyroptosis RCD cell swelling; membrane permeabilization/rupture; DNA condensation/ fragmentation Immunogenic CASP1, CASP11, GSDMD, NLRs, ALRs
Ferroptosis RCD mitochondrial shrinkage; reduced mitochondrial cristae; mitochondrial membrane rupture Immunogenic System XC−, GPX4, TFRC, ACSL4, LPCAT3, ALOX15, GLS2, DPP4, NCOA4, BAP1, BECN1, PEBP1, CARS, VDAC2/3, RAB7A, HSP90, ALK4/5
Parthanatos RCD chromatin condensation; DNA fragmentation; membrane rupture; inconsistent mitochondrial membrane; no apoptotic body formation Immunogenic PARP-1, AIFM1, MIF, OGG1
Anoikis RCD cell shrinkage/rounding; nuclear condensation/fragmentation; nuclear membrane rupture; membrane blebbing; apoptotic body formation; detachment from substrate/other cells Tolerogenic/immunogenic Death receptors, BAX, BAK, AIF, caspases 2, 3, 6, 7, 8, and 9
MPT-driven necrosis RCD similar to necrosis; loss of mitochondrial inner membrane impermeability; mitochondrial membrane dissipation/breakdown Immunogenic CYPD (PPIF)
Entotic cell death

(Entosis)		 RCD cell-in-cell formation Tolerogenic/immunogenic RhoA, ROCKI/II, E-cadherin, α-catenin, actomyosin, LC3, ATGs
Neutrophil extracellular trap cell death (NETosis) RCD membrane rupture; nuclear membrane dissolvement; chromatin decondensation/release Tolerogenic/immunogenic NOX4, PAD4, ELANE, MMP, MPO, ELANE, MMP, MPO
Lysosome-dependent cell death

(LDCD)		 RCD lysosome/plasma membrane rupture Immunogenic BECN1, Na+/K+-ATPase, AMPK, Ras-like protein A
Autophagy-dependent cell death (ADCD) RCD vacuolization (large intracellular vesicles); enlargement of cell organelles; depletion of cell organelles Immunogenic UKL1, PI3KIII, ATGs, LC3
Autosis RCD enhanced cell-substrate adherence; ER fragmentation/breakdown; cell swelling; chromatin condensation Immunogenic Na+/K+-ATPase
Alkaliptosis RCD similar to necrosis Immunogenic IKBKB, NF-κB
Oxeiptosis RCD similar to apoptosis Tolerogenic KEAP1, PGAM5, AIFM1
ACD, accidental cell death; ER, endoplasmic reticulum; MPT, mitochondrial permeability transition; RCD, regulated cell death.

References

  1. Lucillia Bezu; Ligia C. Gomes-De-Silva; Heleen Dewitte; Karine Breckpot; Jitka Fucikova; Radek Spisek; Lorenzo Galluzzi; Oliver Kepp; Guido Kroemer; Combinatorial Strategies for the Induction of Immunogenic Cell Death. Frontiers in Immunology 2015, 6, 187, 10.3389/fimmu.2015.00187.
  2. Francesca Pentimalli; Sandro Grelli; Nicola Di Daniele; Gerry Melino; Ivano Amelio; Cell death pathologies: targeting death pathways and the immune system for cancer therapy. Genes & Immunity 2018, 20, 539-554, 10.1038/s41435-018-0052-x.
  3. Dmitri Krysko; Abhishek Garg; Agnieszka Kaczmarek; Olga Krysko; Patrizia Agostinis; Peter Vandenabeele; Immunogenic cell death and DAMPs in cancer therapy. Nature Cancer 2012, 12, 860-875, 10.1038/nrc3380.
  4. Lorenzo Galluzzi; Aitziber Buqué; Oliver Kepp; Lorenzo Galluzzi Aitziber Buqué Laurence Zitvogel; Guido Kroemer; Immunogenic cell death in cancer and infectious disease. Nature Reviews Immunology 2016, 17, 97-111, 10.1038/nri.2016.107.
  5. Irena Adkins; Lenka Sadilkova; Nada Hradilova; Jakub Tomala; Marek Kovar; Radek Spisek; Severe, but not mild heat-shock treatment induces immunogenic cell death in cancer cells. OncoImmunology 2017, 6, e1311433-e1311433, 10.1080/2162402x.2017.1311433.
  6. Alfonso Serrano-Del Valle; Alberto Anel; Javier Naval; Isabel Marzo; Immunogenic Cell Death and Immunotherapy of Multiple Myeloma. Frontiers in Cell and Developmental Biology 2019, 7, 50, 10.3389/fcell.2019.00050.
  7. Lorenzo Galluzzi; Ilio Vitale; Stuart A. Aaronson; John M. Abrams; Dieter Adam; Patrizia Agostinis; Emad S. Alnemri; Lucia Altucci; Ivano Amelio; David W. Andrews; et al.Margherita Annicchiarico-PetruzzelliAlexey V. AntonovEli AramaEric H. BaehreckeNickolai A. BarlevNicolas G. BazanFrancesca BernassolaMathieu J. M. BertrandKatiuscia BianchiMikhail V. BlagosklonnyKlas BlomgrenChristoph BornerPatricia BoyaCatherine BrennerMichelangelo CampanellaEleonora CandiDidac Carmona-GutierrezFrancesco CecconiFrancis K.-M. ChanNavdeep S. ChandelEmily H. ChengJerry E. ChipukJohn A. CidlowskiAaron CiechanoverGerald M. CohenMarcus ConradJuan R. Cubillos-RuizPeter CzabotarVincenzo D’AngiolellaTed M. DawsonValina L. DawsonVincenzo De LaurenziRuggero De MariaKlaus-Michael DebatinRalph J. DeBerardinisMohanish DeshmukhNicola Di DanieleFrancesco Di VirgilioVishva M. DixitScott J. DixonColin S. DuckettBrian D. DynlachtWafik S. El-DeiryJohn W. ElrodGian Maria FimiaSimone FuldaAna J. García-SáezAbhishek GargCarmen GarridoEvripidis GavathiotisPierre GolsteinEyal GottliebDouglas R. GreenLloyd A. GreeneHinrich GronemeyerAtan GrossGyorgy HajnoczkyJ. Marie HardwickIsaac S. HarrisMichael HengartnerClaudio HetzHidenori IchijoMarja JäätteläBertrand JosephPhilipp J. JostPhilippe P. JuinWilliam J. KaiserMichael KarinThomas KaufmannOliver KeppAdi KimchiRichard N. KitsisDaniel J. KlionskyRichard A. KnightSharad KumarSam W. LeeJohn J. LemastersBeth LevineAndreas LinkermannStuart A. LiptonRichard A. LockshinCarlos López-OtínScott W. LoweTom LueddeEnrico LugliMarion MacFarlaneFrank MadeoMichal MalewiczWalter MalorniGwenola ManicJean-Christophe MarineSeamus J. MartinJean-Claude MartinouJan Paul MedemaPatrick MehlenPascal MeierSonia MelinoEdward A. MiaoJeffery D. MolkentinUte M. MollCristina Muñoz-PinedoShigekazu NagataGabriel NuñezAndrew OberstMoshe OrenMichael OverholtzerMichele PaganoTheocharis PanaretakisManolis PasparakisJosef PenningerDavid M. PereiraShazib PervaizMarcus E. PeterMauro PiacentiniPaolo PintonJochen H.M. PrehnHamsa PuthalakathGabriel A. RabinovichMarkus RehmRosario RizzutoCecilia M.P. RodriguesDavid C. RubinszteinThomas RudelKevin M. RyanEmre SayanLuca ScorranoFeng ShaoYufang ShiJohn SilkeHans-Uwe SimonAntonella SistiguBrent R. StockwellAndreas StrasserGyorgy SzabadkaiStephen W.G. TaitDaolin TangNektarios TavernarakisAndrew ThorburnYoshihide TsujimotoBoris TurkTom Vanden BerghePeter VandenabeeleMatthew G. Vander HeidenAndreas VillungerHerbert W. VirginKaren H. VousdenDomagoj VucicErwin F. WagnerHenning WalczakDavid WallachYing WangJames A. WellsWill WoodJunying YuanZahra ZakeriBoris ZhivotovskyLaurence ZitvogelGerry MelinoGuido Kroemer Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death & Differentiation 2018, 25, 486-541, 10.1038/s41418-017-0012-4.
  8. Ivan Poon; Christopher Lucas; Adriano G. Rossi; Kodi Ravichandran; Apoptotic cell clearance: basic biology and therapeutic potential. Nature Reviews Immunology 2014, 14, 166-180, 10.1038/nri3607.
  9. Nader Yatim; Hélène Jusforgues-Saklani; Susana Orozco; Oliver Schulz; Rosa Barreira da Silva; Caetano Reis e Sousa; Douglas R. Green; Andrew Oberst; Matthew L. Albert; RIPK1 and NF-κB signaling in dying cells determines cross-priming of CD8 + T cells. Science 2015, 350, 328-334, 10.1126/science.aad0395.
  10. Dmitri V. Krysko; Peter Vandenabeele; Clearance of dead cells: mechanisms, immune responses and implication in the development of diseases. Apoptosis 2010, 15, 995-997, 10.1007/s10495-010-0524-6.
  11. Lynda M. Stuart; Mark Lucas; Cathy Simpson; Jonathan Lamb; John Savill; Adam Lacy-Hulbert; Inhibitory Effects of Apoptotic Cell Ingestion upon Endotoxin-Driven Myeloid Dendritic Cell Maturation. The Journal of Immunology 2002, 168, 1627-1635, 10.4049/jimmunol.168.4.1627.
  12. Reinhard E. Voll; Martin Herrmann; Edith A. Roth; Christian Stach; Joachim R. Kalden; Irute Girkontaite; Immunosuppressive effects of apoptotic cells. Nature 1997, 390, 350-351, 10.1038/37022.
  13. Nader Yatim; Hélène Jusforgues-Saklani; Susana Orozco; Oliver Schulz; Rosa Barreira da Silva; Caetano Reis e Sousa; Douglas R. Green; Andrew Oberst; Matthew L. Albert; RIPK1 and NF-κB signaling in dying cells determines cross-priming of CD8 + T cells. Science 2015, 350, 328-334, 10.1126/science.aad0395.
  14. Abhishek D. Garg; Dominika Nowis; Jakub Golab; Peter Vandenabeele; Dmitri V. Krysko; Patrizia Agostinis; Immunogenic cell death, DAMPs and anticancer therapeutics: An emerging amalgamation. Biochimica et Biophysica Acta 2010, 1805, 53-71, 10.1016/j.bbcan.2009.08.003.
  15. Michel Obeid; Antoine Tesniere; Francois Ghiringhelli; Gian Maria Fimia; Lionel Apetoh; Jean-Luc Perfettini; Maria Castedo; Grégoire Mignot; Theocharis Panaretakis; Noelia Casares; et al.Didier MétivierNathanael LarochettePeter van EndertFabiola CiccosantiMauro PiacentiniLaurence ZitvogelGuido Kroemer Calreticulin exposure dictates the immunogenicity of cancer cell death. Nature Medicine 2006, 13, 54-61, 10.1038/nm1523.
  16. Lorenzo Galluzzi; Juliette Humeau; Aitziber Buqué; Laurence Zitvogel; Guido Kroemer; Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors. Nature Reviews Clinical Oncology 2020, 17, 725-741, 10.1038/s41571-020-0413-z.
  17. Guido Kroemer; Claudia Galassi; Laurence Zitvogel; Lorenzo Galluzzi; Immunogenic cell stress and death. Nature Immunology 2022, 23, 487-500, 10.1038/s41590-022-01132-2.
  18. Davide Bedognetti; Society For Immunotherapy Of Cancer (Sitc) Cancer Immune Responsiveness Task Force And Working Groups; Michele Ceccarelli; Lorenzo Galluzzi; Rongze Lu; Karolina Palucka; Josue Samayoa; Stefani Spranger; Sarah Warren; Kwok Kin Wong; et al.Elad ZivDiego ChowellLisa M. CoussensDaniel D. De CarvalhoDavid G. DeNardoJérôme GalonHoward L. KaufmanTomas KirchhoffMichael T. LotzeJason J. LukeAndy J. MinnKaterina PolitiLeonard D. ShultzRichard SimonVésteinn ThórssonJoanne B. WeidhaasMaria Libera AsciertoPaolo Antonio AsciertoJames M. BarnesValentin BarsanPraveen K. BommareddyAdrian BotSarah E. ChurchGennaro CilibertoAndrea De MariaDobrin DraganovWinson S. HoHeather McGeeAnne MonetteJoseph F. MurphyPaola NisticòWungki ParkMaulik PatelMichael QuigleyLaszlo RadvanyiHarry RaftopoulosNils-Petter RudqvistAlexandra SnyderRandy F. SweisSara ValpioneRoberta ZappasodiLisa H. ButterfieldMary L. DisisBernard A. FoxAlessandra CesanoFrancesco M. Marincola Correction to: Toward a comprehensive view of cancer immune responsiveness: a synopsis from the SITC workshop. Journal for ImmunoTherapy of Cancer 2019, 7, 167, 10.1186/s40425-019-0640-y.
  19. Jitka Fucikova; Oliver Kepp; Lenka Kasikova; Giulia Petroni; Takahiro Yamazaki; Peng Liu; Liwei Zhao; Radek Spisek; Guido Kroemer; Lorenzo Galluzzi; et al. Detection of immunogenic cell death and its relevance for cancer therapy. Cell Death & Disease 2020, 11, 1-13, 10.1038/s41419-020-03221-2.
  20. Simone Fulda; Klaus‐Michael Debatin; Apoptosis Signaling in Tumor Therapy. Annals of the New York Academy of Sciences 2004, 1028, 150-156, 10.1196/annals.1322.016.
  21. S Fulda; K-M Debatin; Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 2006, 25, 4798-4811, 10.1038/sj.onc.1209608.
  22. Henning Walczak; Peter H. Krammer; The CD95 (APO-1/Fas) and the TRAIL (APO-2L) Apoptosis Systems. Experimental Cell Research 2000, 256, 58-66, 10.1006/excr.2000.4840.
  23. Xavier Saelens; Nele Festjens; Lieselotte Vande Walle; Maria van Gurp; Geert van Loo; Peter Vandenabeele; Toxic proteins released from mitochondria in cell death. Oncogene 2004, 23, 2861-2874, 10.1038/sj.onc.1207523.
  24. Nader Yatim; Sean Cullen; Matthew L. Albert; Dying cells actively regulate adaptive immune responses. Nature Reviews Immunology 2017, 17, 262-275, 10.1038/nri.2017.9.
  25. Matthew L. Albert; Birthe Sauter; Nina Bhardwaj; Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 1998, 392, 86-89, 10.1038/32183.
  26. Pisana Moroni Rawson; Caroline Molette; Melissa Videtta; Laura Altieri; Debora Franceschini; Tiziana Donato; Luigi Finocchi; Antonella Propato; Marino Paroli; Francesca Meloni; et al.Claudio Maria MastroianniGabriella D'ettorreJohn SidneyAlessandro SetteVincenzo Barnaba Cross-presentation of caspase-cleaved apoptotic self antigens in HIV infection. Nature Medicine 2007, 13, 1431-1439, 10.1038/nm1679.
  27. Douglas R. Green; Thomas Ferguson; Laurence Zitvogel; Guido Kroemer; Immunogenic and tolerogenic cell death. Nature Reviews Immunology 2009, 9, 353-363, 10.1038/nri2545.
  28. Noelia Casares; Marie O. Pequignot; Antoine Tesniere; François Ghiringhelli; Stéphan Roux; Nathalie Chaput; Elise Schmitt; Ahmed Hamai; Sandra Hervas-Stubbs; Michel Obeid; et al.Frédéric CoutantDidier MétivierEvelyne PichardPierre AucouturierGérard PierronCarmen GarridoLaurence ZitvogelGuido Kroemer Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death. Journal of Experimental Medicine 2005, 202, 1691-1701, 10.1084/jem.20050915.
  29. Jaba Gamrekelashvili; Tamar Kapanadze; Miaojun Han; Josef Wissing; Chi Ma; Lothar Jaensch; Michael P. Manns; Todd Armstrong; Elizabeth Jaffee; Ayla O. White; et al.Deborah E. CitrinFirouzeh KorangyTim F. Greten Peptidases released by necrotic cells control CD8+ T cell cross-priming. Journal of Clinical Investigation 2013, 123, 4755-4768, 10.1172/jci65698.
  30. Dominique Vercammen; Greet Brouckaert; Geertrui Denecker; Marc Van De Craen; Wim Declercq; Walter Fiers; Peter Vandenabeele; Dual Signaling of the Fas Receptor: Initiation of Both Apoptotic and Necrotic Cell Death Pathways. Journal of Experimental Medicine 1998, 188, 919-930, 10.1084/jem.188.5.919.
  31. William J Kaiser; Jason W Upton; Edward S Mocarski; Viral modulation of programmed necrosis. Current Opinion in Virology 2013, 3, 296-306, 10.1016/j.coviro.2013.05.019.
  32. Lieselotte Vande Walle; Mohamed Lamkanfi; Pyroptosis. Current Biology 2016, 26, R568-R572, 10.1016/j.cub.2016.02.019.
  33. Luigi Franchi; Tatjana Eigenbrod; Raúl Muñoz-Planillo; Gabriel Nuñez; The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nature Immunology 2009, 10, 241-247, 10.1038/ni.1703.
  34. Lu Liu; Bingwei Sun; Neutrophil pyroptosis: new perspectives on sepsis. Cellular and Molecular Life Sciences 2019, 76, 2031-2042, 10.1007/s00018-019-03060-1.
  35. Brent R. Stockwell; Jose Pedro Friedmann Angeli; Hülya Bayir; Ashley Bush; Marcus Conrad; Scott J. Dixon; Simone Fulda; Sergio Gascón; Stavroula Hatzios; Valerian E. Kagan; et al.Kay NoelXuejun JiangAndreas LinkermannMaureen E. MurphyMichael OverholtzerAtsushi OyagiGabriela PagnussatJason ParkQitao RanCraig S. RosenfeldKonstantin SalnikowDaolin TangFrank M. TortiSuzy V. TortiShinya ToyokuniK.A. WoerpelDonna D. Zhang Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. Cell 2017, 171, 273-285, 10.1016/j.cell.2017.09.021.
  36. Howard O Fearnhead; Peter Vandenabeele; Tom Vanden Berghe; How do we fit ferroptosis in the family of regulated cell death?. Cell Death & Differentiation 2017, 24, 1991-1998, 10.1038/cdd.2017.149.
  37. Yitian Sun; Peng Chen; Bingtao Zhai; Mingming Zhang; Yu Xiang; Jiaheng Fang; Sinan Xu; Yufei Gao; Xin Chen; Xinbing Sui; et al.Guoxiong Li The emerging role of ferroptosis in inflammation. Biomedicine & Pharmacotherapy 2020, 127, 110108, 10.1016/j.biopha.2020.110108.
  38. Jing-Jie Peng; Wei-Tao Song; Fei Yao; Xuan Zhang; Jun Peng; Xiu-Ju Luo; Xiao-Bo Xia; Involvement of regulated necrosis in blinding diseases: Focus on necroptosis and ferroptosis. Experimental Eye Research 2020, 191, 107922, 10.1016/j.exer.2020.107922.
  39. Karen Kate David; Shaida Ahmad Andrabi; Ted Murray Dawson; Valina Lynn Dawson; Parthanatos, a messenger of death. Frontiers in Bioscience 2009, ume, 1116-28, 10.2741/3297.
  40. Nirmal Robinson; Raja Ganesan; Csaba Hegedűs; Katalin Kovács; Thomas A. Kufer; László Virág; Programmed necrotic cell death of macrophages: Focus on pyroptosis, necroptosis, and parthanatos. Redox Biology 2019, 26, 101239, 10.1016/j.redox.2019.101239.
  41. G Kroemer; W S El-Deiry; P Golstein; Marcus Ernst Peter; David Vaux; Peter Vandenabeele; Boris Zhivotovsky; M V Blagosklonny; W Malorni; R A Knight; et al.M PiacentiniShigekazu NagataG Melino Classification of cell death: recommendations of the Nomenclature Committee on Cell Death. Cell Death & Differentiation 2005, 12, 1463-1467, 10.1038/sj.cdd.4401724.
  42. Ge Yan; Mohamed Elbadawi; Thomas Efferth; Multiple cell death modalities and their key features (Review). World Academy of Sciences Journal 2020, 2, 39-48, 10.3892/wasj.2020.40.
  43. Daolin Tang; Rui Kang; Tom Vanden Berghe; Peter Vandenabeele; Guido Kroemer; The molecular machinery of regulated cell death. Cell Research 2019, 29, 347-364, 10.1038/s41422-019-0164-5.
  44. Shida Yousefi; Darko Stojkov; Nina Germic; Dagmar Simon; Xiaoliang Wang; Charaf Benarafa; Hans‐Uwe Simon; Untangling “NETosis” from NETs. European Journal of Immunology 2019, 49, 221-227, 10.1002/eji.201747053.
  45. Y Liu; B Levine; Autosis and autophagic cell death: the dark side of autophagy. Cell Death & Differentiation 2014, 22, 367-376, 10.1038/cdd.2014.143.
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