Viral subversion of immunogenic cell death

Kepp, Oliver; Senovilla, Laura; Galluzzi, Lorenzo; Panaretakis, Theocharis; Tesnière, Antoine; Schlemmer, F.; Madeo, Frank; Zitvogel, Laurence; Kroemer, Guido

doi:10.4161/cc.8.6.7939

Cited by 63 publications

(56 citation statements)

References 76 publications

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“…In accord with this speculation, there is ample evidence that pathogenic viruses can manipulate RIP3-dependent necroptosis, 57,58 perhaps as a strategy for immune escape. In this regard, it should be noted that viruses also subvert pathways linked to ICD including caspase-8 activation, 59 endoplasmic reticulum stress, 60 autophagy, 61 and type-1 IFN responses. 62 Successful anticancer chemotherapeutic agents induce all these hallmarks of ICD, suggesting that they induce a sort of 'viral mimicry'.…”

Section: Discussionmentioning

confidence: 99%

Contribution of RIP3 and MLKL to immunogenic cell death signaling in cancer chemotherapy

Yang¹,

Ma²,

Guo³

et al. 2016

OncoImmunology

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155

145

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Chemotherapy 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 can contribute to ICD signaling and tumor immunogenicity.

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Section: Discussionmentioning

confidence: 99%

Contribution of RIP3 and MLKL to immunogenic cell death signaling in cancer chemotherapy

Yang¹,

Ma²,

Guo³

et al. 2016

OncoImmunology

Self Cite

155

145

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“…Importantly, intratumoral CVB3 administration can prominently recruit cytolytic degranulation marker CD107a-mobilized NK cells and granulocytes, and mature DCs into the tumor bed ( Figure 1). 9,27 As pathogenic viruses have developed their strategies to subvert ecto-CRT and circumvent ICD induction, 109 it is noteworthy that CVB3 infection can induce ecto-CRT accompanied by other DAMPs. 9 Furthermore, we demonstrated that both NK cells and granulocytes substantially contributed to the CVB3-mediated antitumor efficacy as evidenced by in vivo depletion assays.…”

Section: Damps Induced By Infection With Oncolytic Virusesmentioning

confidence: 99%

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

2013

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Apoptotic cell death generally characterized by a morphologically homogenous entity has been considered to be essentially non-immunogenic. However, apoptotic cancer cell death, also known as type 1 programmed cell death (PCD), was recently found to be immunogenic after treatment with several chemotherapeutic agents and oncolytic viruses through the emission of various danger-associated molecular patterns (DAMPs). Extensive studies have revealed that two different types of immunogenic cell death (ICD) inducers, recently classified by their distinct actions in endoplasmic reticulum (ER) stress, can reinitiate immune responses suppressed by the tumor microenvironment. Indeed, recent clinical studies have shown that several immunotherapeutic modalities including therapeutic cancer vaccines and oncolytic viruses, but not conventional chemotherapies, culminate in beneficial outcomes, probably because of their different mechanisms of ICD induction. Furthermore, interests in PCD of cancer cells have shifted from its classical form to novel forms involving autophagic cell death (ACD), programmed necrotic cell death (necroptosis), and pyroptosis, some of which entail immunogenicity after anticancer treatments. In this review, we provide a brief outline of the well-characterized DAMPs such as calreticulin (CRT) exposure, high-mobility group protein B1 (HMGB1), and adenosine triphosphate (ATP) release, which are induced by the morphologically distinct types of cell death. In the latter part, our review focuses on how emerging oncolytic viruses induce different forms of cell death and the combinations of oncolytic virotherapies with further immunomodulation by cyclophosphamide and other immunotherapeutic modalities foster dendritic cell (DC)-mediated induction of antitumor immunity. Accordingly, it is increasingly important to fully understand how and which ICD inducers cause multimodal ICD, which should aid the design of reasonably multifaceted anticancer modalities to maximize ICD-triggered antitumor immunity and eliminate residual or metastasized tumors while sparing autoimmune diseases.

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“…During apoptosis, CALR translocates to the cell surface, where it acts as a signal to promote phagocytosis by surrounding cells (121). Viruses may disrupt this process in order to prevent destruction of the infected cell (122).…”

Section: Fig 3 Enriched Annotation Terms and Pathways Among The Hummentioning

confidence: 99%

A Physical Interaction Network of Dengue Virus and Human Proteins

Khadka

Vangeloff

Zhang

et al. 2011

Molecular & Cellular Proteomics

155

148

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Dengue virus (DENV), an emerging mosquito-transmitted pathogen capable of causing severe disease in humans, interacts with host cell factors to create a more favorable environment for replication. However, few interactions between DENV and human proteins have been reported to date. To identify DENV-human protein interactions, we used high-throughput yeast two-hybrid assays to screen the 10 DENV proteins against a human liver activation domain library. From 45 DNA-binding domain clones containing either full-length viral genes or partially overlapping gene fragments, we identified 139 interactions between DENV and human proteins, the vast majority of which are novel. These interactions involved 105 human proteins, including six previously implicated in DENV infection and 45 linked to the replication of other viruses. Human proteins with functions related to the complement and coagulation cascade, the centrosome, and the cytoskeleton were enriched among the DENV interaction partners. To determine if the cellular proteins were required for DENV infection, we used small interfering RNAs to inhibit their expression. Six of 12 proteins targeted (CALR, DDX3X, ERC1, GOLGA2, TRIP11, and UBE2I) caused a significant decrease in the replication of a DENV replicon. We further showed that calreticulin colocalized with viral dsRNA and with the viral NS3 and NS5 proteins in DENV-infected cells, consistent with a direct role for calreticulin in DENV replication. Human proteins that interacted with DENV had significantly higher average degree and betweenness than expected by chance, which provides additional support for the hypothesis that viruses preferentially target cellular proteins that occupy central position in the human protein interaction network. This study provides a valuable starting point for additional investigations into the roles of human proteins in

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Viral subversion of immunogenic cell death

Cited by 63 publications

References 76 publications

Contribution of RIP3 and MLKL to immunogenic cell death signaling in cancer chemotherapy

Contribution of RIP3 and MLKL to immunogenic cell death signaling in cancer chemotherapy

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

A Physical Interaction Network of Dengue Virus and Human Proteins

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