The Experts below are selected from a list of 3348 Experts worldwide ranked by ideXlab platform
Guido Kroemer - One of the best experts on this subject based on the ideXlab platform.
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trial watch chemotherapy induced Immunogenic Cell Death in immuno oncology
OncoImmunology, 2020Co-Authors: Isaure Vanmeerbeek, Jitka Fucikova, Radek Spisek, Guido Kroemer, Jenny Sprooten, Dirk De Ruysscher, Sabine Tejpar, Peter Vandenberghe, Laurence Zitvogel, Lorenzo GalluzziAbstract:The term ‘Immunogenic Cell Death’ (ICD) denotes an immunologically unique type of regulated Cell Death that enables, rather than suppresses, T Cell-driven immune responses that are specific for ant...
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clinical evidence that Immunogenic Cell Death sensitizes to pd 1 pd l1 blockade
OncoImmunology, 2019Co-Authors: Oliver Kepp, Laurence Zitvogel, Guido KroemerAbstract:ABSTRACTIn preclinical in vivo models of cancer, the induction of Immunogenic Cell Death (ICD) sensitizes to subsequent immunotherapy. Several clinical trials now confirm that pretreatment with ICD...
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assessment of annexin a1 release during Immunogenic Cell Death
Methods in Enzymology, 2019Co-Authors: Elisa Elena Baracco, Adriana Petrazzuolo, Guido KroemerAbstract:Abstract The protein annexin A1 (ANXA1) belongs to the danger-associated molecular patterns (DAMPs) that alert the innate immune system about tissue perturbations. In the context of Immunogenic Cell Death (ICD), ANXA1 is released from the cytoplasm of dying Cells and, once extraCellular, acts on formyl peptide receptor 1 (FPR1) expressed on dendritic Cells to favor long-term interactions between dying and dendritic Cells. As a result, the accumulation of extraCellular ANXA1 constitutes one of the hallmarks of ICD. In the past, the detection of ANXA1 was based on semiquantitative immunoblots. More recently, a commercial enzyme-linked immunosorbent assay (ELISA) has been developed to measure ANXA1 in an accurate fashion. Here, we detail the protocol to measure the concentration of ANXA1 in the supernatants of cancer Cells treated with chemotherapy.
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quantitation of calreticulin exposure associated with Immunogenic Cell Death
Methods in Enzymology, 2019Co-Authors: Liwei Zhao, Oliver Kepp, Guido KroemerAbstract:Abstract Tumor Cells treated by Immunogenic Cell Death (ICD) inducers emit danger associated molecular patterns (DAMP), including but not limited to calreticulin (CALR), which translocates from the ER lumen to the surface of the Cellular membrane where it serves as de novo uptake signal for antigen presenting Cells of the immune system. CALR is exposed at an early stage of ICD and dictates tumor antigen transfer and therefore the Immunogenicity of cancer Cell Death. Here, we provide a bi-color flow cytometry protocol for the quantification of ICD-associated CALR Cell surface exposure in fixed samples. As compared to the detection of surface exposed CALR by confocal microscopy, the present flow cytometry-based analysis is cost-efficient and does not require sophisticated equipment. Moreover, the staining panel can be extended to a multicolor analysis for the parallel assessment of additional parameters.
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methods for measuring hmgb1 release during Immunogenic Cell Death
Methods in Enzymology, 2019Co-Authors: Liwei Zhao, Oliver Kepp, Guido KroemerAbstract:Abstract The exodus of the alarmin high mobility group box 1 (HMGB1) from the nucleus constitutes a crucial Cellular danger signal and manifests as a sequential process in which HMGB1 first exits the nucleus into the cytoplasm and then is secreted or passively released through the permeabilized plasma membrane. ExtraCellular HMGB1 can interact with pattern recognition receptors to stimulate innate immune responses. Here, we describe a discovery pipeline for the identification of pharmacological agents endowed with HMGB1 releasing properties. The “retention using selective hooks” (RUSH) system in which a streptavidin-NLS3 fusion protein serves as a nuclear hook to sequester streptavidin-binding peptide (SBP) fused with HMGB1 and green fluorescent protein (GFP) allowed for synchronizing HMGB1 increase. Thus, exclusively in the presence of biotin, which liberates HMGB1-SBP-GFP from its nuclear hook, Immunogenic Cell Death (ICD) inducers such as anthracyclines are able to cause the nucleo-cytoplasmic translocation of HMGB1-SBP-GFP. This system facilitates the identification of HMGB1 releasing agents in medium- to high-throughput screening assays.
Lorenzo Galluzzi - One of the best experts on this subject based on the ideXlab platform.
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Immunogenic Cell Death Driven by Radiation-Impact on the Tumor Microenvironment.
Cancer treatment and research, 2020Co-Authors: Takahiro Yamazaki, Sandra Demaria, Claire Vanpouille-box, Lorenzo GalluzziAbstract:Immunogenic Cell Death (ICD) is a particular form of Cell Death that can initiate adaptive immunity against antigens expressed by dying Cells in the absence of exogenous adjuvants. This implies that Cells undergoing ICD not only express antigens that are not covered by thymic tolerance, but also deliver adjuvant-like signals that enable the recruitment and maturation of antigen-presenting Cells toward an immunostimulatory phenotype, culminating with robust cross-priming of antigen-specific CD8+ T Cells. Such damage-associated molecular patterns (DAMPs), which encompass Cellular proteins, small metabolites and cytokines, are emitted in a spatiotemporally defined manner in the context of failing adaptation to stress. Radiation therapy (RT) is a bona fide inducer of ICD, at least when employed according to specific doses and fractionation schedules. Here, we discuss the mechanisms whereby DAMPs emitted by cancer Cells undergoing RT-driven ICD alter the functional configuration of the tumor microenvironment.
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consensus guidelines for the definition detection and interpretation of Immunogenic Cell Death
Journal for ImmunoTherapy of Cancer, 2020Co-Authors: Lorenzo Galluzzi, Patrizia Agostinis, Sandy Adjemian, Ilio Vitale, Sarah Warren, Aitziber Buque Martinez, Timothy A Chan, George Coukos, Sandra Demaria, Eric DeutschAbstract:Cells succumbing to stress via regulated Cell Death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intraCellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of Immunogenic Cell Death (ICD), discuss the key factors that dictate the ability of dying Cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.
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trial watch chemotherapy induced Immunogenic Cell Death in immuno oncology
OncoImmunology, 2020Co-Authors: Isaure Vanmeerbeek, Jitka Fucikova, Radek Spisek, Guido Kroemer, Jenny Sprooten, Dirk De Ruysscher, Sabine Tejpar, Peter Vandenberghe, Laurence Zitvogel, Lorenzo GalluzziAbstract:The term ‘Immunogenic Cell Death’ (ICD) denotes an immunologically unique type of regulated Cell Death that enables, rather than suppresses, T Cell-driven immune responses that are specific for ant...
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methods to detect Immunogenic Cell Death in vivo
Methods of Molecular Biology, 2020Co-Authors: Takahiro Yamazaki, Lorenzo Galluzzi, Aitziber Buque, Marissa Rybstein, Jonathan M Chen, Ai SatoAbstract:In response to selected stressors, cancer Cells can undergo a form of regulated Cell Death that-in immunocompetent syngeneic hosts-is capable of eliciting an adaptive immune response specific for dead Cell-associated antigens. Thus, such variant of regulated Cell Death manifests with robust antigenicity and adjuvanticity. As compared to their normal counterparts, malignant Cells are highly antigenic per se, implying that they express a variety of antigens that are not covered by central tolerance. However, the precise modality through which cancer Cells die in response to stress has a major influence on adjuvanticity. Moreover, the adjuvanticity threshold to productively drive anticancer immune responses is considerably lower in tumor-naive hosts as compared to their tumor-bearing counterparts, largely reflecting the establishment of peripheral tolerance to malignant lesions in the latter (but not in the former). So far, no Cellular biomarker or combination thereof has been found to reliably predict the ability of cancer Cell Death to initiate antitumor immunity. Thus, although some surrogate biomarkers of adjuvanticity can be used for screening purposes, the occurrence of bona fide Immunogenic Cell Death (ICD) can only be ascertained in vivo. Here, we describe two methods that can be harnessed to straightforwardly determine the Immunogenicity of mouse cancer Cells succumbing to stress in both tumor-naive and tumor-bearing hosts.
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trial watch Immunogenic Cell Death induction by anticancer chemotherapeutics
OncoImmunology, 2017Co-Authors: Abhishek D Garg, Guido Kroemer, Patrizia Agostinis, Laurence Zitvogel, Sanket More, Nicole Rufo, Odeta Mece, Maria Livia Sassano, Lorenzo GalluzziAbstract:The expression “Immunogenic Cell Death” (ICD) refers to a functionally unique form of Cell Death that facilitates (instead of suppressing) a T Cell-dependent immune response specific for dead Cell-derived antigens. ICD critically relies on the activation of adaptive responses in dying Cells, culminating with the exposure or secretion of immunostimulatory molecules commonly referred to as “damage-associated molecular patterns”. Only a few agents can elicit bona fide ICD, including some clinically established chemotherapeutics such as doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin. In this Trial Watch, we discuss recent progress on the development of ICD-inducing chemotherapeutic regimens, focusing on studies that evaluate clinical efficacy in conjunction with immunological biomarkers.
Laurence Zitvogel - One of the best experts on this subject based on the ideXlab platform.
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trial watch chemotherapy induced Immunogenic Cell Death in immuno oncology
OncoImmunology, 2020Co-Authors: Isaure Vanmeerbeek, Jitka Fucikova, Radek Spisek, Guido Kroemer, Jenny Sprooten, Dirk De Ruysscher, Sabine Tejpar, Peter Vandenberghe, Laurence Zitvogel, Lorenzo GalluzziAbstract:The term ‘Immunogenic Cell Death’ (ICD) denotes an immunologically unique type of regulated Cell Death that enables, rather than suppresses, T Cell-driven immune responses that are specific for ant...
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clinical evidence that Immunogenic Cell Death sensitizes to pd 1 pd l1 blockade
OncoImmunology, 2019Co-Authors: Oliver Kepp, Laurence Zitvogel, Guido KroemerAbstract:ABSTRACTIn preclinical in vivo models of cancer, the induction of Immunogenic Cell Death (ICD) sensitizes to subsequent immunotherapy. Several clinical trials now confirm that pretreatment with ICD...
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eif2α phosphorylation is pathognomonic for Immunogenic Cell Death
Cell Death & Differentiation, 2018Co-Authors: Lucillia Bezu, Laurence Zitvogel, Allan Sauvat, Juliette Humeau, Liwei Zhao, Kristina Iribarren, Sabrina Forveille, Ligia C Gomesdasilva, Pauline GarciaAbstract:The phosphorylation of eIF2α is essential for the endoplasmic reticulum (ER) stress response, the formation of stress granules, as well as macroautophagy. Several successful anticancer chemotherapeutics have the property to induce Immunogenic Cell Death (ICD), thereby causing anticancer immune responses. ICD is accompanied by the translocation of calreticulin (CALR) from the ER lumen to the plasma membrane, which facilitates the transfer of tumor-associated antigens to dendritic Cells. Here we systematically investigated the capacity of anticancer chemotherapeutics to induce signs of ER stress. ICD inducers including anthracyclines and agents that provoke tetraploidization were highly efficient in enhancing the phosphorylation of eIF2α, yet failed to stimulate other signs of ER stress including the transcriptional activation of activating transcription factor 4 (ATF4), the alternative splicing of X-box binding protein 1 (XBP1s) mRNA and the proteolytic cleavage of activating transcription factor 6 (ATF6) both in vitro and in cancers established in mice. Systematic analyses of clinically used anticancer chemotherapeutics revealed that only eIF2α phosphorylation, but none of the other signs of ER stress, correlated with CALR exposure. eIF2α phosphorylation induced by mitoxantrone, a prototype ICD-inducing anthracyline, was mediated by eIF2α kinase-3 (EIF2AK3). Machine-learning approaches were used to determine the physicochemical properties of drugs that induce ICD, revealing that the sole ER stress response relevant to the algorithm is eIF2α phosphorylation with its downstream consequences CALR exposure, stress granule formation and autophagy induction. Importantly, this approach could reduce the complexity of compound libraries to identify ICD inducers based on their physicochemical and structural characteristics. In summary, it appears that eIF2α phosphorylation constitutes a pathognomonic characteristic of ICD.
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trial watch Immunogenic Cell Death induction by anticancer chemotherapeutics
OncoImmunology, 2017Co-Authors: Abhishek D Garg, Guido Kroemer, Patrizia Agostinis, Laurence Zitvogel, Sanket More, Nicole Rufo, Odeta Mece, Maria Livia Sassano, Lorenzo GalluzziAbstract:The expression “Immunogenic Cell Death” (ICD) refers to a functionally unique form of Cell Death that facilitates (instead of suppressing) a T Cell-dependent immune response specific for dead Cell-derived antigens. ICD critically relies on the activation of adaptive responses in dying Cells, culminating with the exposure or secretion of immunostimulatory molecules commonly referred to as “damage-associated molecular patterns”. Only a few agents can elicit bona fide ICD, including some clinically established chemotherapeutics such as doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin. In this Trial Watch, we discuss recent progress on the development of ICD-inducing chemotherapeutic regimens, focusing on studies that evaluate clinical efficacy in conjunction with immunological biomarkers.
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Immunogenic Cell Death in cancer and infectious disease
Nature Reviews Immunology, 2017Co-Authors: Lorenzo Galluzzi, Oliver Kepp, Laurence Zitvogel, Aitziber Buque, Guido KroemerAbstract:Initiation of an adaptive immune response depends on the detection of both antigenic epitopes and adjuvant signals. Infectious pathogens and cancer Cells often avoid immune detection by limiting the release of danger signals from dying Cells. When is Cell Death Immunogenic and what are the pathophysiological implications of this process? The Immunogenicity of Cell Death is determined by its antigenicity and its adjuvanticity. Cells infected by pathogens as well as cancer Cells exhibit accrued antigenicity. Stress responses in dying Cells cause the emission of adjuvant-like danger signals. Different sets of danger signals are associated with distinct variants of Immunogenic Cell Death. Both pathogens and cancer Cells interrupt danger signalling for their own benefit. Reinstating the Immunogenicity of Cell Death holds promise for anticancer therapy. Immunogenicity depends on two key factors: antigenicity and adjuvanticity. The presence of exogenous or mutated antigens explains why infected Cells and malignant Cells can initiate an adaptive immune response provided that the Cells also emit adjuvant signals as a consequence of Cellular stress and Death. Several infectious pathogens have devised strategies to control Cell Death and limit the emission of danger signals from dying Cells, thereby avoiding immune recognition. Similarly, cancer Cells often escape immunosurveillance owing to defects in the molecular machinery that underlies the release of endogenous adjuvants. Here, we review current knowledge on the mechanisms that underlie the activation of immune responses against dying Cells and their pathophysiological relevance.
Oliver Kepp - One of the best experts on this subject based on the ideXlab platform.
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clinical evidence that Immunogenic Cell Death sensitizes to pd 1 pd l1 blockade
OncoImmunology, 2019Co-Authors: Oliver Kepp, Laurence Zitvogel, Guido KroemerAbstract:ABSTRACTIn preclinical in vivo models of cancer, the induction of Immunogenic Cell Death (ICD) sensitizes to subsequent immunotherapy. Several clinical trials now confirm that pretreatment with ICD...
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quantitation of calreticulin exposure associated with Immunogenic Cell Death
Methods in Enzymology, 2019Co-Authors: Liwei Zhao, Oliver Kepp, Guido KroemerAbstract:Abstract Tumor Cells treated by Immunogenic Cell Death (ICD) inducers emit danger associated molecular patterns (DAMP), including but not limited to calreticulin (CALR), which translocates from the ER lumen to the surface of the Cellular membrane where it serves as de novo uptake signal for antigen presenting Cells of the immune system. CALR is exposed at an early stage of ICD and dictates tumor antigen transfer and therefore the Immunogenicity of cancer Cell Death. Here, we provide a bi-color flow cytometry protocol for the quantification of ICD-associated CALR Cell surface exposure in fixed samples. As compared to the detection of surface exposed CALR by confocal microscopy, the present flow cytometry-based analysis is cost-efficient and does not require sophisticated equipment. Moreover, the staining panel can be extended to a multicolor analysis for the parallel assessment of additional parameters.
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quantification of eif2alpha phosphorylation during Immunogenic Cell Death
Methods in Enzymology, 2019Co-Authors: Lucillia Bezu, Guido Kroemer, Juliette Humeau, Alejandra Wu Chuang, Oliver KeppAbstract:Abstract Immunogenic Cell Death (ICD) is a particular modality of Cell Death that can be triggered by selected anticancer chemotherapeutics. Tumor Cells undergoing ICD can induce an adaptive anticancer immune response that targets residual cancer Cells with the same antigenic profile. The activation of a full-blown immune response against the tumor antigen is preceded by the release or exposure of danger associated molecular patterns (DAMPs) by tumor Cells that stimulate the attraction, activation and maturation of dendritic Cells and eventually the antigen-specific priming of cytotoxic T lymphocytes (CTLs). The phosphorylation of the eukaryotic translation initiation factor (EIF2A) is a pathognomonic characteristic of ICD, which governs the release/exposure of DAMPs such as ATP and calreticulin and thus the Immunogenicity of Cell Death. Here we describe techniques to detect eIF2alpha phosphorylation for the assessment of ICD.
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methods for measuring hmgb1 release during Immunogenic Cell Death
Methods in Enzymology, 2019Co-Authors: Liwei Zhao, Oliver Kepp, Guido KroemerAbstract:Abstract The exodus of the alarmin high mobility group box 1 (HMGB1) from the nucleus constitutes a crucial Cellular danger signal and manifests as a sequential process in which HMGB1 first exits the nucleus into the cytoplasm and then is secreted or passively released through the permeabilized plasma membrane. ExtraCellular HMGB1 can interact with pattern recognition receptors to stimulate innate immune responses. Here, we describe a discovery pipeline for the identification of pharmacological agents endowed with HMGB1 releasing properties. The “retention using selective hooks” (RUSH) system in which a streptavidin-NLS3 fusion protein serves as a nuclear hook to sequester streptavidin-binding peptide (SBP) fused with HMGB1 and green fluorescent protein (GFP) allowed for synchronizing HMGB1 increase. Thus, exclusively in the presence of biotin, which liberates HMGB1-SBP-GFP from its nuclear hook, Immunogenic Cell Death (ICD) inducers such as anthracyclines are able to cause the nucleo-cytoplasmic translocation of HMGB1-SBP-GFP. This system facilitates the identification of HMGB1 releasing agents in medium- to high-throughput screening assays.
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eif2α phosphorylation a hallmark of Immunogenic Cell Death
OncoImmunology, 2018Co-Authors: Lucillia Bezu, Oliver Kepp, Allan Sauvat, Juliette Humeau, Marion Leduc, Guido KroemerAbstract:Immunogenic Cell Death (ICD) induced by anticancer chemotherapeutics is usually preceded by premortem stress affecting the endoplasmic reticulum (ER). This ER stress does not reflect a canonical unfolded protein response (UPR) but rather manifests solely at the level of the phosphorylation of eIF2α. eIF2α phosphorylation is hence a quintessential hallmark of ICD that can be detected by immunohistochemistry in tumor samples.
Erika Vacchelli - One of the best experts on this subject based on the ideXlab platform.
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contribution of rip3 and mlkl to Immunogenic Cell Death signaling in cancer chemotherapy
OncoImmunology, 2016Co-Authors: Heng Yang, Allan Sauvat, Erika Vacchelli, Takahiro Yamazaki, Heng Zhou, Guo Chen, Christophe Klein, Federico Pietrocola, Sylvie Souquere, Laurence ZitvogelAbstract:ABSTRACTChemotherapy can reinstate anticancer immunosurveillance through inducing tumor Immunogenic Cell Death (ICD). Here, we show that anthracyclines and oxaliplatin can trigger necroptosis in murine cancer Cell lines expressing receptor-interacting serine-threonine kinase 3 (RIP3) and mixed lineage kinase domain-like (MLKL). Necroptotic Cells featured biochemical hallmarks of ICD and stimulated anticancer immune responses in vivo. Chemotherapy normally killed Rip3−/− and Mlkl−/− tumor Cells and normally induced caspase-3 activation in such Cells, yet was unable to reduce their growth in vivo. RIP3 or MLKL deficiency abolished the capacity of dying cancer Cells to elicit an immune response. This could be attributed to reduced release of ATP and high mobility group box 1 (HMGB1) by RIP3 and MLKL-deficient Cells. Measures designed to compensate for deficient ATP and HMGB1 signaling restored the chemotherapeutic response of Rip3−/− and Mlkl−/− cancers. Altogether, these results suggest that RIP3 and MLKL c...
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trial watch Immunogenic Cell Death inducers for anticancer chemotherapy
OncoImmunology, 2015Co-Authors: Erika Vacchelli, Jitka Fucikova, Radek Spisek, Jerome Galon, Fernando Aranda, Francesca Castoldi, Alexander Eggermont, Isabelle Cremer, Catherine Sautesfridman, Eric TartourAbstract:The term “Immunogenic Cell Death” (ICD) is now employed to indicate a functionally peculiar form of apoptosis that is sufficient for immunocompetent hosts to mount an adaptive immune response against dead Cell-associated antigens. Several drugs have been ascribed with the ability to provoke ICD when employed as standalone therapeutic interventions. These include various chemotherapeutics routinely employed in the clinic (e.g., doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin) as well as some anticancer agents that are still under preclinical or clinical development (e.g., some microtubular inhibitors of the epothilone family). In addition, a few drugs are able to convert otherwise non-Immunogenic instances of Cell Death into bona fide ICD, and may therefore be employed as chemotherapeutic adjuvants within combinatorial regimens. This is the case of cardiac glycosides, like digoxin and digitoxin, and zoledronic acid. Here, we discuss recent developm...
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consensus guidelines for the detection of Immunogenic Cell Death
OncoImmunology, 2014Co-Authors: Oliver Kepp, Lionel Apetoh, Patrizia Agostinis, Sandy Adjemian, Erika Vacchelli, Ilio Vitale, Laura Senovilla, Fernando Aranda, Vincenzo Barnaba, Norma BloyAbstract: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.
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crosstalk between er stress and Immunogenic Cell Death
Cytokine & Growth Factor Reviews, 2013Co-Authors: Oliver Kepp, Laurie Menger, Erika Vacchelli, Clara LocherAbstract:Abstract Preclinical and clinical findings suggest that tumor-specific immune responses may be responsible – at least in part – for the clinical success of therapeutic regimens that rely on Immunogenic Cell Death (ICD) inducers, including anthracyclines and oxaliplatin. The molecular pathways whereby some, but not all, cytotoxic agents promote bona fide ICD remain to be fully elucidated. Nevertheless, a central role for the endoplasmic reticulum (ER) stress response has been revealed in all scenarios of ICD described thus far. Hence, components of the ER stress machinery may constitute clinically relevant druggable targets for the induction of ICD. In this review, we will summarize recent findings in the field of ICD research with a special focus on ER stress mechanisms and their implication for cancer therapy.
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Trial watch: Chemotherapy with Immunogenic Cell Death inducers.
Oncoimmunology, 2013Co-Authors: Erika Vacchelli, Guido Kroemer, Laurence Zitvogel, Laura Senovilla, Wolf Hervé Fridman, Jerome Galon, Alexander Eggermont, Lorenzo GalluzziAbstract:It is now clear that the immune system plays a critical role not only during oncogenesis and tumor progression, but also as established neoplastic lesions respond to therapy. Selected cytotoxic chemicals can indeed elicit Immunogenic Cell Death, a functionally peculiar type of apoptosis that stimulates tumor-specific cognate immune responses. Such Immunogenic chemotherapeutics include cyclophosphamide, doxorubicin and oxaliplatin (which are approved by FDA for the treatment of various hematological and solid malignancies), mitoxantrone (which is currently employed both as an anticancer agent and against multiple sclerosis) and patupilone (a microtubular poison in clinical development). One year ago, in the second issue of OncoImmunology, we discussed the scientific rationale behind Immunogenic chemotherapy and reviewed the status of recent clinical trials investigating the off-label use of cyclophosphamide, doxorubicin, oxaliplatin and mitoxantrone in cancer patients. Here, we summarize the latest developments in this area of clinical research, covering both high-impact studies that have been published during the last 13 months and clinical trials that have been initiated in the same period to assess the antineoplastic profile of Immunogenic chemotherapeutics.
