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20 results on '"Vacchelli, Erika"'

1. A loss-of-function polymorphism in ATG16L1 compromises therapeutic outcome in head and neck carcinoma patients.

Author

Le Naour, Julie, Sztupinszki, Zsofia, Carbonnier, Vincent, Casiraghi, Odile, Marty, Virginie, Galluzzi, Lorenzo, Szallasi, Zoltan, Kroemer, Guido, and Vacchelli, Erika

Subjects
CROHN'S disease, PATTERN perception receptors, HEAD & neck cancer, SINGLE nucleotide polymorphisms, CELL morphology, SQUAMOUS cell carcinoma
Abstract

The anticancer immune response is shaped by immunogenic cell stress and death pathways. Thus, cancer cells can release danger-associated molecular patterns that act on pattern recognition receptors expressed by dendritic cells and their precursors to elicit an antitumor immune response. Here, we investigated the impact of single nucleotide polymorphisms (SNPs) in genes affecting this cancer-immunity dialogue in the context of head and neck squamous cell carcinoma (HNSCC). We observed that homozygosity for a loss-of-function SNP (rs2241880, leading to the substitution of a threonine residue in position 300 by an alanine) affecting autophagy related 16 like 1 (ATG16L1) is coupled to poor progression-free survival in platinum-treated HNSCC patients. This result was obtained on a cohort of patients enrolled at the Gustave Roussy Cancer Campus and was validated on an independent cohort of The Cancer Genome Atlas (TCGA). Homozygosity in rs2241880 is well known to predispose to Crohn's disease, and epidemiological associations between Crohn's disease and HNSCC have been reported at the levels of cancer incidence and prognosis. We speculate that rs2241880 might be partially responsible for this association. [ABSTRACT FROM AUTHOR]

Published
2022
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2. Systemic autophagy in the therapeutic response to anthracycline-based chemotherapy

Author

Castoldi, Francesca, Vacchelli, Erika, Zitvogel, Laurence, Maiuri, Maria Chiara, Pietrocola, Federico, and Kroemer, Guido

Subjects
lcsh:Immunologic diseases. Allergy, fasting, immunogenic cell death, immunotherapy, lcsh:RC581-607, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, lcsh:RC254-282, mitoxantrone, Original Research, Cancer
Abstract

The success of chemotherapy largely depends on the anticancer immune response triggered by tumor cells that succumb to immunogenic cell death (ICD). One of the hallmarks of ICD is premortem autophagy that facilitates the release of adenosine triphosphate from dying cancer cells and acts as a chemoattractant for dendritic cell precursors. Here, we show that the immune response induced by inoculation of cancer cells undergoing ICD in response to the anthracycline mitoxantrone (MTX) can be improved by a short-term fasting regimen (48 hours of starvation) and that this effect is reversed by systemic administration of the autophagy inhibitor dimethyl α-ketoglutarate. Tumor growth reduction by MTX treatment is known to depend on autophagy induction in cancer cells as well as on an intact immune system. We compared the antitumor effects of MTX on autophagy-competent cancers implanted in wild type (WT) or partially autophagy-deficient (Becn1± or Atg4b−/-) mice. While there was no difference in the tumor growth reducing effects of MTX on tumors evolving in WT, Becn1+/- and Atg4b−/- mice, we observed an increase in the toxicity of MTX on Atg4b−/- mice. These results suggest that autophagy in cancer cells (but less so in host cells) is rate-limiting for therapeutically relevant anticancer immune responses, yet has a major role in blunting the life-threatening toxicity of chemotherapy.

Published
2018

3. Trial Watch: experimental TLR7/TLR8 agonists for oncological indications.

Author

Frega, Giorgio, Wu, Qi, Le Naour, Julie, Vacchelli, Erika, Galluzzi, Lorenzo, Kroemer, Guido, and Kepp, Oliver

Subjects
GENITAL warts, TYPE I interferons, ACTINIC keratosis, TOLL-like receptors, ANTINEOPLASTIC agents
Abstract

Resiquimod (R848) and motolimod (VTX-2337) are second-generation experimental derivatives of imiquimod, an imidazoquinoline with immunostimulatory properties originally approved by the US Food and Drug Administration for the topical treatment of actinic keratosis and genital warts more than 20 years ago. Both resiquimod and motolimod operate as agonists of Toll-like receptor 7 (TLR7) and/or TLR8, in thus far delivering adjuvant-like signals to antigen-presenting cells (APCs). In line with such an activity, these compounds are currently investigated as immunostimulatory agents for the treatment of various malignancies, especially in combination with peptide-based, dendritic cell-based, cancer cell lysate-based, or DNA-based vaccines. Here, we summarize preclinical and clinical evidence recently collected to support the development of resiquimod and motolimod and other TLR7/TLR8 agonists as anticancer agents. [ABSTRACT FROM AUTHOR]

Published
2020
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4. Contribution of annexin A1 to anticancer immunosurveillance.

Author

Baracco, Elisa Elena, Stoll, Gautier, Van Endert, Peter, Zitvogel, Laurence, Vacchelli, Erika, and Kroemer, Guido

Subjects
CYTOTOXIC T cells, RENAL cancer, RECOMBINANT proteins, CANCER cells, CANCER chemotherapy
Abstract

Mouse cancers lacking the expression of annexin A1 (ANXA1) fail to respond to immunogenic chemotherapies. This has been initially explained by the requirement of extracellular ANXA1 (which is released from dying cancer cells) to engage formyl peptide receptor-1 (FPR1) on dendritic cells (DC) for the establishment of corpse/DC synapses. Here, we show that ANXA1-deficent cancer cells exhibit a defect in the exposure of calreticulin (CALR), which is an important "eat-me" signal, facilitating the phagocytic uptake of dead-cell antigens by DC. Of note, intratumoral injection of recombinant CALR protein was able to restore the therapeutic response of ANXA1-deficient cancers to anthracycline-based chemotherapy. Carcinomas developing in patients tend to downregulate ANXA1 expression as compared to their normal tissues of origin. ANXA1-low breast, colorectal, lung and kidney cancers are scarcely infiltrated by DC and cytotoxic T lymphocytes, supporting the idea that ANXA1 deficiency facilitates immune escape. We propose that such ANXA1-low cancers might be particularly suitable to local immunotherapy with CALR protein. [ABSTRACT FROM AUTHOR]

Published
2019
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5. Trial Watch

Author

Vacchelli, Erika, Vitale, Ilio, Tartour, Eric, Eggermont, Alexander, Sautès-Fridman, Catherine, Galon, Jérôme, Zitvogel, Laurence, Kroemer, Guido, and Galluzzi, Lorenzo

Subjects
electroporation, Salmonella typhimurium, brachytherapy, stereotactic radiosurgery, Saccharomyces cerevisiae, Review, stereotactic body radiation therapy, agatolimod, CpG-7909, resiquimod, immunogenic cell death, mucosal immunity, dendritic cells, MYD88, intensity-modulated radiation therapy, radionuclide, VTX-2337, TRIF, cross-presentation
Abstract

Radiotherapy has extensively been employed as a curative or palliative intervention against cancer throughout the last century, with a varying degree of success. For a long time, the antineoplastic activity of X- and γ-rays was entirely ascribed to their capacity of damaging macromolecules, in particular DNA, and hence triggering the (apoptotic) demise of malignant cells. However, accumulating evidence indicates that (at least part of) the clinical potential of radiotherapy stems from cancer cell-extrinsic mechanisms, including the normalization of tumor vasculature as well as short- and long-range bystander effects. Local bystander effects involve either the direct transmission of lethal signals between cells connected by gap junctions or the production of diffusible cytotoxic mediators, including reactive oxygen species, nitric oxide and cytokines. Conversely, long-range bystander effects, also known as out-of-field or abscopal effects, presumably reflect the elicitation of tumor-specific adaptive immune responses. Ionizing rays have indeed been shown to promote the immunogenic demise of malignant cells, a process that relies on the spatiotemporally defined emanation of specific damage-associated molecular patterns (DAMPs). Thus, irradiation reportedly improves the clinical efficacy of other treatment modalities such as surgery (both in neo-adjuvant and adjuvant settings) or chemotherapy. Moreover, at least under some circumstances, radiotherapy may potentiate anticancer immune responses as elicited by various immunotherapeutic agents, including (but presumably not limited to) immunomodulatory monoclonal antibodies, cancer-specific vaccines, dendritic cell-based interventions and Toll-like receptor agonists. Here, we review the rationale of using radiotherapy, alone or combined with immunomodulatory agents, as a means to elicit or boost anticancer immune responses, and present recent clinical trials investigating the therapeutic potential of this approach in cancer patients.

Published
2012

6. Trial watch

Author

Aranda, Fernando, Vacchelli, Erika, Obrist, Florine, Eggermont, Alexander, Galon, Jérôme, Hervé Fridman, Wolf, Cremer, Isabelle, Tartour, Eric, Zitvogel, Laurence, Kroemer, Guido, and Galluzzi, Lorenzo

Subjects
CD19, chimeric antigen receptor, peripheral blood lymphocytes, plasmacytoid dendritic cells, cytokine-induced killer cells, immunogenic cell death, antigen-presenting cells, interleukin-2, Review, monoclonal antibodies, regulatory T cells, Toll-like receptors
Abstract

Dendritic cells (DCs) occupy a privileged position at the interface between innate and adaptive immunity, orchestrating a large panel of responses to both physiological and pathological cues. In particular, whereas the presentation of antigens by immature DCs generally results in the development of immunological tolerance, mature DCs are capable of priming robust, and hence therapeutically relevant, adaptive immune responses. In line with this notion, functional defects in the DC compartment have been shown to etiologically contribute to pathological conditions including (but perhaps not limited to) infectious diseases, allergic and autoimmune disorders, graft rejection and cancer. Thus, the possibility of harnessing the elevated immunological potential of DCs for anticancer therapy has attracted considerable interest from both researchers and clinicians over the last decade. Alongside, several methods have been developed not only to isolate DCs from cancer patients, expand them, load them with tumor-associated antigens and hence generate highly immunogenic clinical grade infusion products, but also to directly target DCs in vivo. This intense experimental effort has culminated in 2010 with the approval by the US FDA of a DC-based preparation (sipuleucel-T, Provenge®) for the treatment of asymptomatic or minimally symptomatic metastatic castration-refractory prostate cancer. As an update to the latest Trial Watch dealing with this exciting field of research (October 2012), here we summarize recent advances in DC-based anticancer regimens, covering both high-impact studies that have been published during the last 13 mo and clinical trials that have been launched in the same period to assess the antineoplastic potential of this variant of cellular immunotherapy.

Published
2013

7. Trial Watch Dendritic cell-based interventions for cancer therapy.

Author

Vacchelli, Erika, Vitale, Ilio, Eggermont, Alexander, Fridman, Wolf Hervé, Fučíková, Jitka, Cremer, Isabelle, Galon, Jérôme, Tartour, Eric, Zitvogel, Laurence, Kroemer, Guido, and Galluzzi, Lorenzo

Subjects
*DENDRITIC cells, *AUTOIMMUNE diseases, *CANCER patients, *CANCER treatment, *PATHOLOGY
Abstract

Dendritic cells (DCs) occupy a privileged position at the interface between innate and adaptive immunity, orchestrating a large panel of responses to both physiological and pathological cues. In particular, whereas the presentation of antigens by immature DCs generally results in the development of immunological tolerance, mature DCs are capable of priming robust, and hence therapeutically relevant, adaptive immune responses. In line with this notion, functional defects in the DC compartment have been shown to etiologically contribute to pathological conditions including (but perhaps not limited to) infectious diseases, allergic and autoimmune disorders, graft rejection and cancer. Thus, the possibility of harnessing the elevated immunological potential of DCs for anticancer therapy has attracted considerable interest from both researchers and clinicians over the last decade. Alongside, several methods have been developed not only to isolate DCs from cancer patients, expand them, load them with tumorassociated antigens and hence generate highly immunogenic clinical grade infusion products, but also to directly target DCs in vivo. This intense experimental efort has culminated in 2010 with the approval by the US FDA of a DC-based preparation (sipuleucel-T, Provenge®) for the treatment of asymptomatic or minimally symptomatic metastatic castration-refractory prostate cancer. As an update to the latest Trial watch dealing with this exciting ield of research (October 2012), here we summarize recent advances in DC-based anticancer regimens, covering both high-impact studies that have been published during the last 13 mo and clinical trials that have been launched in the same period to assess the antineoplastic potential of this variant of cellular immunotherapy. [ABSTRACT FROM AUTHOR]

Published
2013
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8. Trial Watch: Anticancer radioimmunotherapy.

Author

Vacchelli, Erika, Vitale, Ilio, Tartour, Eric, Eggermont, Alexander, Sautès-Fridman, Catherine, Galon, Jérôme, Zitvogel, Laurence, Kroemer, Guido, and Galluzzi, Lorenzo

Subjects
*RADIOIMMUNOTHERAPY, *ANTINEOPLASTIC agents, *REACTIVE oxygen species, *NITRIC oxide, *RADIOBIOLOGY, *CANCER patients, *INTENSITY modulated radiotherapy, *STEREOTACTIC radiosurgery
Abstract

Radiotherapy has extensively been employed as a curative or palliative intervention against cancer throughout the last century, with a varying degree of success. For a long time, the antineoplastic activity of X- and γ-rays was entirely ascribed to their capacity of damaging macromolecules, in particular DNA, and hence triggering the (apoptotic) demise of malignant cells. However, accumulating evidence indicates that (at least part of) the clinical potential of radiotherapy stems from cancer cell-extrinsic mechanisms, including the normalization of tumor vasculature as well as short- and long-range bystander effects. Local bystander effects involve either the direct transmission of lethal signals between cells connected by gap junctions or the production of diffusible cytotoxic mediators, including reactive oxygen species, nitric oxide and cytokines. Conversely, long-range bystander effects, also known as out-of-field or abscopal effects, presumably reflect the elicitation of tumor-specific adaptive immune responses. Ionizing rays have indeed been shown to promote the immunogenic demise of malignant cells, a process that relies on the spatiotemporally defined emanation of specific damage-associated molecular patterns (DAMPs). Thus, irradiation reportedly improves the clinical efficacy of other treatment modalities such as surgery (both in neo-adjuvant and adjuvant settings) or chemotherapy. Moreover, at least under some circumstances, radiotherapy may potentiate anticancer immune responses as elicited by various immunotherapeutic agents, including (but presumably not limited to) immunomodulatory monoclonal antibodies, cancer-specific vaccines, dendritic cell-based interventions and Toll-like receptor agonists. Here, we review the rationale of using radiotherapy, alone or combined with immunomodulatory agents, as a means to elicit or boost anticancer immune responses, and present recent clinical trials investigating the therapeutic potential of this approach in cancer patients. [ABSTRACT FROM AUTHOR]

Published
2013
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9. Trial watch: Cardiac glycosides and cancer therapy.

Author

Menger, Laurie, Vacchelli, Erika, Kepp, Oliver, Eggermont, Alexander, Tartour, Eric, Zitvogel, Laurence, Kroemer, Guido, and Lorenzo Galluzzi

Subjects
*CARDIAC glycosides, *CARDIAC contraction, *CANCER immunotherapy, *CELL membranes, *HEART cells, *CANCER cells, *CELLULAR immunity, *ARRHYTHMIA, *THERAPEUTICS, *PHYSIOLOGY
Abstract

Cardiac glycosides (CGs) are natural compounds sharing the ability to operate as potent inhibitors of the plasma membrane Na+/K+-ATPase, hence promoting—via an indirect mechanism—the intracellular accumulation of Ca2+ ions. In cardiomyocytes, increased intracellular Ca2+ concentrations exert prominent positive inotropic effects, that is, they increase myocardial contractility. Owing to this feature, two CGs, namely digoxin and digitoxin, have extensively been used in the past for the treatment of several cardiac conditions, including distinct types of arrhythmia as well as contractility disorders. Nowadays, digoxin is approved by the FDA and indicated for the treatment of congestive heart failure, atrial fibrillation and atrial flutter with rapid ventricular response, whereas the use of digitoxin has been discontinued in several Western countries. Recently, CGs have been suggested to exert potent antineoplastic effects, notably as they appear to increase the immunogenicity of dying cancer cells. In this Trial Watch, we summarize the mechanisms that underpin the unsuspected anticancer potential of CGs and discuss the progress of clinical studies that have evaluated/are evaluating the safety and efficacy of CGs for oncological indications. [ABSTRACT FROM AUTHOR]

Published
2013
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10. Loss-of-function alleles of P2RX7 and TLR4 fail to affect the response to chemotherapy in non-small cell lung cancer.

Author

Vacchelli, Erika, Galluzzi, Lorenzo, Rousseau, Vanessa, Rigoni, Alice, Tesnière, Antoine, Delahaye, Nicolas F., Schlemmer, Frédéric, Menger, Laurie, Qader Sukkurwala, Abdul, Adjemian, Sandy, Martins, Isabelle, Michaud, Mickaël, Dunant, Ariane, Kepp, Oliver, Brambilla, Elisabeth, Soria, Jean-Charles, Zitvogel, Laurence, and Kroemer, Guido

Abstract

The success of anticancer chemotherapy relies at least in part on the induction of an immune response against tumor cells. Thus, tumors growing on mice that lack the pattern recognition receptor TLR4 or the purinergic receptor P2RX7 fail to respond to chemotherapy with anthracyclins or oxaliplatin in conditions in which the same neoplasms growing on immunocompetent mice would do so. Similarly, the therapeutic efficacy (measured as progression-free survival) of adjuvant chemotherapy with anthracyclins is reduced in breast cancer patients bearing loss-of-function alleles of TLR4 or P2RX7. TLR4 loss-of-function alleles also have a negative impact on the therapeutic outcome of oxaliplatin in colorectal cancer patients. Here, we report that loss-of-function TLR4 and P2RX7 alleles do not affect overall survival in non-small cell lung cancer (NSCLC) patients, irrespective of the administration and type of chemotherapy. The intrinsic characteristics of NSCLC (which near-to-always is chemoresistant and associated with poor prognosis) and/or the type of therapy that is employed to treat this malignancy (which near-to-always is based on cisplatin) may explain why two genes that affect the immune response to dying cells fail to influence the clinical progression of NSCLC patients. [ABSTRACT FROM AUTHOR]

Published
2012
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11. ATP-dependent recruitment, survival and differentiation of dendritic cell precursors in the tumor bed after anticancer chemotherapy.

Author

Yuting Ma, Adjemian, Sandy, Heng Yang, Portela Catani, João Paulo, Hannani, Dalil, Martins, Isabelle, Michaud, Mickaël, Kepp, Oliver, Qader Sukkurwala, Abdul, Vacchelli, Erika, Galluzzi, Lorenzo, Zitvogel, Laurence, and Kroemer, Guido

Subjects
ADENOSINE triphosphate, DENDRITIC cells, CANCER chemotherapy, TUMOR antigens, EXTRACELLULAR enzymes
Abstract

Tumor cells succumb to chemotherapy while releasing ATP. We have found that extracellular ATP attracts dendritic cell (DC) precursors into the tumor bed, facilitates their permanence in the proximity of dying cells and promotes their differentiation into mature DCs endowed with the capacity of presenting tumor-associated antigens. [ABSTRACT FROM AUTHOR]

Published
2013
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12. Anticancer activity of cardiac glycosides At the frontier between cell-autonomous and immunological effects.

Author

Kepp, Oliver, Menger, Laurie, Vacchelli, Erika, Adjemian, Sandy, Martins, Isabelle, Yuting Ma, Sukkurwala, Abdul Qader, Michaud, Mickaël, Galluzzi, Lorenzo, Zitvogel, Laurence, and Kroemer, Guido

Subjects
CARDIAC glycosides, CANCER prevention, DIGOXIN, IMMUNE response, CANCER cells, DRUG therapy
Abstract

Retrospective clinical data indicate that cardiac glycosides (CGs), notably digoxin, prolong the survival of carcinoma patients treated with conventional chemotherapy. CGs are known to influence the immune response at multiple levels. In addition, recent results suggest that CGs trigger the immunogenic demise of cancer cells, an effect that most likely contributes to their clinical anticancer activity. [ABSTRACT FROM AUTHOR]

Published
2012
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14. Systemic autophagy in the therapeutic response to anthracycline-based chemotherapy.

Author

Castoldi, Francesca, Vacchelli, Erika, Zitvogel, Laurence, Maiuri, Maria Chiara, Pietrocola, Federico, and Kroemer, Guido

Subjects
*CELL death, *TUMOR growth, *CANCER cells, *IMMUNE response, *FASTING, *MITOXANTRONE, *AUTOPHAGY
Abstract

The success of chemotherapy largely depends on the anticancer immune response triggered by tumor cells that succumb to immunogenic cell death (ICD). One of the hallmarks of ICD is premortem autophagy that facilitates the release of adenosine triphosphate from dying cancer cells and acts as a chemoattractant for dendritic cell precursors. Here, we show that the immune response induced by inoculation of cancer cells undergoing ICD in response to the anthracycline mitoxantrone (MTX) can be improved by a short-term fasting regimen (48 hours of starvation) and that this effect is reversed by systemic administration of the autophagy inhibitor dimethyl α-ketoglutarate. Tumor growth reduction by MTX treatment is known to depend on autophagy induction in cancer cells as well as on an intact immune system. We compared the antitumor effects of MTX on autophagy-competent cancers implanted in wild type (WT) or partially autophagy-deficient (Becn1± or Atg4b−/-) mice. While there was no difference in the tumor growth reducing effects of MTX on tumors evolving in WT, Becn1+/- and Atg4b−/- mice, we observed an increase in the toxicity of MTX on Atg4b−/- mice. These results suggest that autophagy in cancer cells (but less so in host cells) is rate-limiting for therapeutically relevant anticancer immune responses, yet has a major role in blunting the life-threatening toxicity of chemotherapy. [ABSTRACT FROM AUTHOR]

Published
2019
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15. The ratio of CD8 /FOXP3 T lymphocytes infiltrating breast tissues predicts the relapse of ductal carcinoma in situ.

Author

Semeraro, Michaela, Adam, Julien, Stoll, Gautier, Louvet, Emilie, Chaba, Kariman, Poirier-Colame, Vichnou, Sauvat, Allan, Senovilla, Laura, Vacchelli, Erika, Bloy, Norma, Humeau, Juliette, Buque, Aitziber, Kepp, Oliver, Zitvogel, Laurence, André, Fabrice, Mathieu, Marie-Christine, Delaloge, Suzette, and Kroemer, Guido

Subjects
CYTOTOXIC T cells, CELL death, PLOIDY, HAPLODIPLOIDY, IMMUNOSUPPRESSIVE agents
Abstract

In a series of 248 tumor samples obtained from image-guided biopsies from patients diagnosed with ductal carcinomain situof the breast, we attempted to identify biomarkers that predict microinfiltration at definitive surgery or relapse during follow-up. For this, we used immunohistochemical methods, followed by automated image analyses, to measure the mean diameter of nuclei (which correlates with ploidy), the phosphorylation of eukaryotic initiation factor 2α (eIF2α, which reflects endoplasmic reticulum stress) as well as the density and ratio of CD8+cytotoxic T lymphocytes and FOXP3+regulatory T cells. The median nuclear diameter of malignant cells correlated with eIF2α phosphorylation (in cancerous tissue), which in turn correlated with the density of the CD8+infiltrate and the CD8+/FOXP3 ratio (both in cancerous and the adjacent non-cancerous parenchyma). Neither microinfiltration nor lymph node involvement was associated with the probability of relapse. Both correlated positively with the CD8+/FOXP3 ratio in the malignant area. In contrast, relapse was associated with a paucity of the CD8+infiltrate as well as an unfavorable CD8+/FOXP3 ratio, both in malignant and non-malignant parenchyma. The combined analysis of the CD8+/FOXP3 ratio in cancerous and non-cancerous tissues revealed a significant impact of their interaction on the probability of relapse, but not on the presence of microinfiltration or lymph node metastasis. Altogether, these results support the idea of an immunosurveillance system that determines the risk of relapse in ductal carcinomain situof the breast. [ABSTRACT FROM PUBLISHER]

Published
2016
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16. Trial Watch: Immunotherapy plus radiation therapy for oncological indications.

Author

Vacchelli, Erika, Bloy, Norma, Aranda, Fernando, Buqué, Aitziber, Cremer, Isabelle, Demaria, Sandra, Eggermont, Alexander, Formenti, Silvia Chiara, Fridman, Wolf Hervé, Fucikova, Jitka, Galon, Jérôme, Spisek, Radek, Tartour, Eric, Zitvogel, Laurence, Kroemer, Guido, and Galluzzi, Lorenzo

Subjects
*CANCER cells, *RADIOTHERAPY, *IMMUNE response, *ANTINEOPLASTIC agents, *IMMUNOTHERAPY
Abstract

Malignant cells succumbing to some forms of radiation therapy are particularly immunogenic and hence can initiate a therapeutically relevant adaptive immune response. This reflects the intrinsic antigenicity of malignant cells (which often synthesize a high number of potentially reactive neo-antigens) coupled with the ability of radiation therapy to boost the adjuvanticity of cell death as it stimulates the release of endogenous adjuvants from dying cells. Thus, radiation therapy has been intensively investigated for its capacity to improve the therapeutic profile of several anticancer immunotherapies, including (but not limited to) checkpoint blockers, anticancer vaccines, oncolytic viruses, Toll-like receptor (TLR) agonists, cytokines, and several small molecules with immunostimulatory effects. Here, we summarize recent preclinical and clinical advances in this field of investigation. [ABSTRACT FROM PUBLISHER]

Published
2016
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17. Yet another pattern recognition receptor involved in the chemotherapy-induced anticancer immune response: Formyl peptide receptor-1.

Author

Vacchelli, Erika, Ma, Yuting, Baracco, Elisa E., Zitvogel, Laurence, and Kroemer, Guido

Subjects
*PATTERN perception receptors, *ANTINEOPLASTIC agents, *CANCER chemotherapy, *IMMUNE response, *PEPTIDE receptors
Abstract

Several pattern recognition receptors including toll-like receptors and purinergic receptors are implicated in the anticancer immune response elicited by anthracyclines or oxaliplatin. Recently, formyl peptide receptor-1 (FPR1) has been involved in this response as well. FPR1 is required for the correct positioning of dendritic cells (DC) close to dying cancer cells. A genetic defect in FPR1 abrogates cross-presentation of tumor antigens by DC, thereby compromising therapy-elicited immunosurveillance. [ABSTRACT FROM AUTHOR]

Published
2016
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18. Immunosurveillance in esophageal carcinoma: The decisive impact of regulatory T cells.

Author

Vacchelli, Erika, Semeraro, Michaela, Adam, Julien, Dartigues, Peggy, Zitvogel, Laurence, and Kroemer, Guido

Subjects
*ESOPHAGEAL cancer, *T cells, *CHEMORADIOTHERAPY, *IMMUNOPATHOLOGY, *ONCOLOGIC surgery
Abstract

Neoadjuvant radiochemotherapy of esophageal carcinomas causes a variable degree of depletion of tumor-infiltrating FOXP3+regulatory T cells (Tregs). The frequency of local Tregs in the operative specimens negatively correlates with the pathological response and overall patient survival. These results underscore the importance of immunosurveillance in determining the fate of patients with esophageal cancers treated with radiochemotherapy. [ABSTRACT FROM AUTHOR]

Published
2016
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19. Caloric Restriction Mimetics Enhance Anticancer Immunosurveillance

Author

Valentina Sica, Frank Madeo, Norma Bloy, Maria Chiara Maiuri, Erika Vacchelli, David Enot, Fernando Aranda, Laura Senovilla, Jonathan Pol, Sarah Levesque, Nicolas Jacquelot, Elisa E. Baracco, Laurence Zitvogel, Lionel Apetoh, Guillermo Mariño, Takahiro Yamazaki, Francesca Castoldi, Aitziber Buqué, Josef M. Penninger, Bernhard Ryffel, Simonetta Falzoni, Beth Levine, Verena Sigl, Sylvère Durand, Sylvie Lachkar, Francesco Di Virgilio, Alexis Chery, Guido Kroemer, Shuan Rao, Federico Pietrocola, Apoptose, cancer et immunité (Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Université Paris Descartes - Paris 5 (UPD5), Centre de Recherche des Cordeliers (CRC), Université Paris-Sud - Paris 11 (UP11), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie et Cancérologie Intégratives (CRC - Inserm U1138), Group of Immune receptors of the Innate and Adaptive System, Institut d’Investigacions Biomédiques August Pi i Sunyer (IDIBAPS), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), RENARD (TGE Réseau National de RPE interdisciplinaire - 3443 ), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Université de Strasbourg (UNISTRA)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Université de Lille-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), LAboratoire de Recherche Historique Rhône-Alpes - UMR5190 (LARHRA), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de pneumologie, oncologie thoracique et soins intensifs respiratoires [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Institute of Molecular Biosciences, Karl-Franzens University Graz, (IMB), Karl-Franzens-Universität Graz, Apoptose, cancer et immunité (U848), Institute of Molecular Biotechnology, Austrian Academy of Sciences (OeAW), Karolinska University Hospital [Stockholm], Service de biologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Lille-Sorbonne Université (SU)-Aix Marseille Université (AMU)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Equipe 11 labellisée pas la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers ( CRC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Gustave Roussy ( IGR ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ), Immunologie des tumeurs et immunothérapie ( UMR 1015 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunologie et Cancérologie Intégratives ( CRC - Inserm U1138 ), Mathématiques Appliquées à Paris 5 ( MAP5 - UMR 8145 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National des Sciences Mathématiques et de leurs Interactions-Centre National de la Recherche Scientifique ( CNRS ), RENARD ( TGE Réseau National de RPE interdisciplinaire ), FR-CNRS 3443, LAboratoire de Recherche Historique Rhône-Alpes - UMR5190 ( LARHRA ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -École normale supérieure - Lyon ( ENS Lyon ) -Université Lumière - Lyon 2 ( UL2 ) -Université Jean Moulin - Lyon III-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Hôpital Charles Nicolle [Rouen]-CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Immunologie et Neurogénétique Expérimentales et Moléculaires ( INEM ), Université d'Orléans ( UO ) -Centre National de la Recherche Scientifique ( CNRS ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Institute of Molecular Biosciences, Karl-Franzens University Graz, ( IMB ), Apoptose, cancer et immunité ( U848 ), Austrian Academy of Sciences ( OeAW ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Apoptose, cancer et immunité ( Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138 ), Institut Gustave Roussy ( IGR ) -Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre National de la Recherche Scientifique ( CNRS ) -Université Jean Moulin - Lyon III ( UJML ) -Université Lumière - Lyon 2 ( UL2 ) -École normale supérieure - Lyon ( ENS Lyon ) -Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Grenoble Alpes ( UGA ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Hôpital Charles Nicolle [Rouen]-CHU Rouen, Pietrocola, Federico, Pol, Jonathan, Vacchelli, Erika, Rao, Shuan, Enot, David P, Baracco, Elisa E, Levesque, Sarah, Castoldi, Francesca, Jacquelot, Nicola, Yamazaki, Takahiro, Senovilla, Laura, Marino, Guillermo, Aranda, Fernando, Durand, Sylvère, Sica, Valentina, Chery, Alexi, Lachkar, Sylvie, Sigl, Verena, Bloy, Norma, Buque, Aitziber, Falzoni, Simonetta, Ryffel, Bernhard, Apetoh, Lionel, Di Virgilio, Francesco, Madeo, Frank, Maiuri, MARIA CHIARA, Zitvogel, Laurence, Levine, Beth, Penninger, Josef M, and Kroemer, Guido

Subjects
0301 basic medicine, Cancer Research, ATP citrate lyase, Spermidine, Bariatric Surgery, immunosurveillance, T-Lymphocytes, Regulatory, Autophagy-Related Protein 5, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, chemistry.chemical_compound, Mice, regulatory T cell, Citrates, 3. Good health, Immunogenic Cell-Death, Immunosurveillance, medicine.anatomical_structure, Oncology, Biochemistry, Differentiation, embryonic structures, Immunogenic cell death, In-Vivo, Human, Regulatory T cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Dietary Restriction, NO, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, Monitoring, Immunologic, In vivo, Cell Line, Tumor, medicine, Autophagy, Animals, Humans, cancer, Chemotherapy, Breast-Cancer, Caloric Restriction, chemotherapy, immunosurveillance, regulatory T cell, Animal, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, regulatory T&nbsp, fungi, Neoplasms, Experimental, cell, Methotrexate, 030104 developmental biology, chemistry, Acetylation, Mutation, Cancer research, Citrate, Neoplasm Transplantation
Abstract

International audience; Caloric restriction mimetics (CRMs) mimic the biochemical effects of nutrient deprivation by reducing lysine acetylation of cellular proteins, thus triggering autophagy. Treatment with the CRM hydroxycitrate, an inhibitor of ATP citrate lyase, induced the depletion of regulatory T cells (which dampen anticancer immunity) from autophagy-competent, but not autophagy-deficient, mutant KRAS-induced lung cancers in mice, thereby improving anticancer immunosurveillance and reducing tumor mass. Short-term fasting or treatment with several chemically unrelated autophagy-inducing CRMs, including hydroxycitrate and spermidine, improved the inhibition of tumor growth by chemotherapy in vivo. This effect was only observed for autophagy-competent tumors, depended on the presence of T lymphocytes, and was accompanied by the depletion of regulatory T cells from the tumor bed.

Published
2016

20. Consensus guidelines for the detection of immunogenic cell death

Author

Kepp, O., Senovilla, L., Vitale, I., Vacchelli, E., Adjemian, S., Agostinis, P., Apetoh, L., Aranda, F., Barnaba, V., Bloy, N., Bracci, L., Breckpot, K., Brough, D., Buqué, A., Castro, Mg, Cirone, M., Colombo, Mi, Cremer, I., Demaria, S., Dini, L., Eliopoulos, A., Faggioni, A., Formenti, Sc, Fu??íková, J., Gabriele, L., Gaipl, Us, Galon, J., Garg, A., Ghiringhelli, F., Giese, Na, Guo, Zs, Hemminki, A., Herrmann, M., Hodge, Jw, Holdenrieder, S., Honeychurch, J., Hm, Hu, Huang, X., Illidge, Tm, Kono, K., Korbelik, M., Krysko, Dv, Loi, S., Lowenstein, Pr, Lugli, E., Ma, Y., Madeo, F., Manfredi, Aa, Martins, I., Matzinger, P., Mavilio, D., Menger, L., Merendino, N., Michaud, M., Mignot, G., Mossman, Kl, Multhoff, G., Oehler, R., Palombo, F., Panaretakis, T., Pol, J., Proietti, E., Ricci, Je, Riganti, Chiara, Rovere Querini, P., Rubartelli, A., Sistigu, A., Smyth, Mj, Sonnemann, J., Spisek, R., Stagg, J., Sukkurwala, Aq, Tartour, E., Thorburn, A., Thorne, Sh, Vandenabeele, P., Velotti, F., Workenhe, Sr, Yang, H., Zong, Wx, Zitvogel, L., Kroemer, G., Galluzzi, L., Medicine and Pharmacy academic/administration, Basic (bio-) Medical Sciences, Laboratory of Molecullar and Cellular Therapy, Chemistry, Kepp, Oliver, Senovilla, Laura, Vitale, Ilio, Vacchelli, Erika, Adjemian, Sandy, Agostinis, Patrizia, Apetoh, Lionel, Aranda, Fernando, Barnaba, Vincenzo, Bloy, Norma, Bracci, Laura, Breckpot, Karine, Brough, David, Buqué, Aitziber, Castro, Maria G, Cirone, Mara, Colombo, Maria I, Cremer, Isabelle, Demaria, Sandra, Dini, Luciana, Eliopoulos, Aristides G, Faggioni, Alberto, Formenti, Silvia C, Fučíková, Jitka, Gabriele, Lucia, Gaipl, Udo S, Galon, Jérôme, Garg, Abhishek, Ghiringhelli, Françoi, Giese, Nathalia A, Guo, Zong Sheng, Hemminki, Akseli, Herrmann, Martin, Hodge, James W, Holdenrieder, Stefan, Honeychurch, Jamie, Hu, Hong Min, Huang, Xing, Illidge, Tim M, Kono, Koji, Korbelik, Mladen, Krysko, Dmitri V, Loi, Sherene, Lowenstein, Pedro R, Lugli, Enrico, Ma, Yuting, Madeo, Frank, Manfredi, Angelo A, Martins, Isabelle, Mavilio, Domenico, Menger, Laurie, Merendino, Nicolò, Michaud, Michael, Mignot, Gregoire, Mossman, Karen L, Multhoff, Gabriele, Oehler, Rudolf, Palombo, Fabio, Panaretakis, Theochari, Pol, Jonathan, Proietti, Enrico, Ricci, Jean Ehrland, Riganti, Chiara, Rovere Querini, Patrizia, Rubartelli, Anna, Sistigu, Antonella, Smyth, Mark J, Sonnemann, Juergen, Spisek, Radek, Stagg, John, Sukkurwala, Abdul Qader, Tartour, Eric, Thorburn, Andrew, Thorne, Stephen H, Vandenabeele, Peter, Velotti, Francesca, Workenhe, Samuel T, Yang, Haining, Zong, Wei Xing, Zitvogel, Laurence, Kroemer, Guido, Galluzzi, Lorenzo, Kepp, O, Senovilla, L, Vitale, I, Vacchelli, E, Adjemian, S, Agostinis, P, Apetoh, L, Aranda, F, Barnaba, V, Bloy, N, Bracci, L, Breckpot, K, Brough, D, Buque, A, Castro, Mg, Cirone, M, Colombo, Mi, Cremer, I, Demaria, S, Dini, L, Eliopoulos, Ag, Faggioni, A, Formenti, Sc, Fucikova, J, Gabriele, L, Gaipl, U, Galon, J, Garg, A, Ghiringhelli, F, Giese, Na, Guo, Z, Hemminki, A, Herrmann, M, Hodge, Jw, Holdenrieder, S, Honeychurch, J, Hu, Hm, Huang, X, Illidge, Tm, Kono, K, Korbelik, M, Krysko, Dv, Loi, S, Lowenstein, Pr, Lugli, E, Ma, Yt, Madeo, F, Manfredi, ANGELO ANDREA M. A., Martins, I, Mavilio, D, Menger, L, Merendino, N, Michaud, M, Mignot, G, Mossman, Kl, Multhoff, G, Oehler, R, Palombo, F, Panaretakis, T, Pol, J, Proietti, E, Ricci, Je, Riganti, C, ROVERE QUERINI, Patrizia, Rubartelli, A, Sistigu, A, Smyth, Mj, Sonnemann, J, Spisek, R, Stagg, J, Sukkurwala, Aq, Tartour, E, Thorburn, A, Thorne, Sh, Vandenabeele, P, Velotti, F, Workenhe, St, Yang, Hn, Zong, Wx, Zitvogel, L, Kroemer, G, and Galluzzi, L.

Subjects
HSV-1, herpes simplex virus type I, Δψm, mitochondrial transmembrane potential, medicine.medical_treatment, DAMP, damage-associated molecular pattern, detection, FLT3LG, fms-related tyrosine kinase 3 ligand, Review, member 3, calreticulin, Eukaryotic translation initiation factor 2A, RFP, red fluorescent protein, 0302 clinical medicine, MOMP, mitochondrial outer membrane permeabilization, Immunology and Allergy, GFP, green fluorescent protein, HMGB1, 0303 health sciences, education.field_of_study, Toll-like receptor, BAK1, BCL2-antagonist/killer 1, H2B, histone 2B, endoplasmic reticulum stre, 3. Good health, BAX, BCL2-associated X protein, XBP1, X-box binding protein 1, cell death, Oncology, PDIA3, protein disulfide isomerase family A, 030220 oncology & carcinogenesis, endoplasmic reticulum stress, Immunogenic cell death, HSP, heat shock protein, immunotherapy, TLR, Toll-like receptor, autophagy, ATF6, activating transcription factor 6, Immunology, ICD, immunogenic cell death, EIF2A, eukaryotic translation initiation factor 2A, Guidelines, Biology, BCL2, B-cell CLL/lymphoma 2 protein, ER, endoplasmic reticulum, PI, propidium iodide, ATP release, 03 medical and health sciences, Immune system, immunogenic, medicine, IFN, interferon, Antigen-presenting cell, education, 030304 developmental biology, CALR, calreticulin, Damage-associated molecular pattern, Immunotherapy, CTL, cytotoxic T lymphocyte, HMGB1, high mobility group box 1, IL, interleukin, G3BP1, GTPase activating protein (SH3 domain) binding protein 1, APC, antigen-presenting cell, Cancer cell, DiOC6(3), 3,3′-dihexyloxacarbocyanine iodide, DAPI, 4′,6-diamidino-2-phenylindole
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. 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

Published
2014

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