Anticancer immunochemotherapy using adjuvants with direct cytotoxic effects
Laurence Zitvogel,Guido Kroemer +1 more
TLDR
The authors show that ligation of viral RNA sensors, such as RIG-I or MDA-5, by viral RNA mimetics triggers mitochondrial apoptosis in human melanoma cells in an IFN-independent fashion, suggesting that tumor cell killing and immunostimulation may synergize for optimal anticancer immunochemotherapy.Abstract:
Conventional chemotherapeutics may induce immunogenic cancer cell death or stimulate immune effectors via so-called off-target effects. The study by Besch et al. in this issue of the JCI now demonstrates that agents designed to stimulate the innate immune system by activating intracellular pattern recognition receptors can kill cancer cells in a direct, cell-autonomous fashion (see the related article beginning on page 2399). The authors show that ligation of viral RNA sensors, such as RIG-I or MDA-5, by viral RNA mimetics triggers mitochondrial apoptosis in human melanoma cells in an IFN-independent fashion. The data suggest that tumor cell killing and immunostimulation may synergize for optimal anticancer immunochemotherapy.read more
Citations
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Cancer immunotherapy comes of age
TL;DR: In the context of advances in the understanding of how tolerance, immunity and immunosuppression regulate antitumour immune responses, these successes suggest that active immunotherapy represents a path to obtain a durable and long-lasting response in cancer patients.
Journal ArticleDOI
Deciphering and reversing tumor immune suppression.
TL;DR: The ways in which tumors exert immune suppression are reviewed and the new therapies that seek to reverse this phenomenon and promote anti-tumor immunity are highlighted.
Journal ArticleDOI
The role of tumour-stromal interactions in modifying drug response: challenges and opportunities.
TL;DR: Progress in in vitro screening platforms as well as orthotopic and 'orthometastatic' xenograft mouse models has enabled comprehensive characterization of the impact of the tumour microenvironment on therapeutic efficacy, which can hopefully bridge the gap between preclinical studies and clinical trials of anticancer agents.
Journal ArticleDOI
Structural Insights into RNA Recognition by RIG-I
Dahai Luo,Steve C. Ding,Adriana Vela,Andrew Kohlway,Brett D. Lindenbach,Anna Marie Pyle,Anna Marie Pyle +6 more
TL;DR: The crystal structure of RIG-I in complex with double-stranded RNA reveals complex interplay between motor domains, accessory mechanical domains, and RNA that has implications for understanding the nanomechanical function of this protein family and other ATPases more broadly.
Journal ArticleDOI
Platinum-based drugs disrupt STAT6-mediated suppression of immune responses against cancer in humans and mice
W. Joost Lesterhuis,Cornelis J. A. Punt,Stanleyson V. Hato,Dagmar Eleveld-Trancikova,Bastiaan J.H. Jansen,Stefan Nierkens,Gerty Schreibelt,Annemiek J. de Boer,Carla M.L. van Herpen,Johannes H.A.M. Kaanders,Johan H. J. M. van Krieken,Gosse J. Adema,Carl G. Figdor,I. Jolanda M. de Vries +13 more
TL;DR: It is concluded that platinum-based anticancer drugs can enhance the immunostimulatory potential of DCs and decrease the immunosuppressive capability of tumor cells.
References
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Principles of Cancer Therapy: Oncogene and Non-oncogene Addiction
TL;DR: Evidence is presented for a large class of non-oncogenes that are essential for cancer cell survival and present attractive drug targets and theoretical considerations for combining orthogonal cancer therapies are provided.
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Immunogenic and tolerogenic cell death
Douglas R. Green,Thomas A. Ferguson,Laurence Zitvogel,Laurence Zitvogel,Guido Kroemer,Guido Kroemer +5 more
TL;DR: A central problem in immunology is to understand how the immune system determines whether cell death is immunogenic, tolerogenic or 'silent', which can result in autoimmunity.
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Mechanisms of pre-apoptotic calreticulin exposure in immunogenic cell death
Theocharis Panaretakis,Theocharis Panaretakis,Theocharis Panaretakis,Oliver Kepp,Oliver Kepp,Oliver Kepp,Ulf Brockmeier,Antoine Tesniere,Antoine Tesniere,Antoine Tesniere,Ann Charlotte Björklund,Daniel C. Chapman,Michael Durchschlag,Nicholas Joza,Nicholas Joza,Nicholas Joza,Gérard Pierron,Peter van Endert,Peter van Endert,Junying Yuan,Laurence Zitvogel,Laurence Zitvogel,Frank Madeo,David B. Williams,Guido Kroemer,Guido Kroemer,Guido Kroemer +26 more
TL;DR: Depletion of PERK, caspase‐8 or SNAREs had no effect on cell death induced by anthracyclines, yet abolished the immunogenicity of cell death, which could be restored by absorbing recombinant CRT to the cell surface.
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Viral evasion and subversion of pattern-recognition receptor signalling
TL;DR: Accumulating evidence on how viral infection and PRR signalling pathways intersect is providing further insights into the function of the pathways involved, their constituent proteins and ways in which they could be manipulated therapeutically.
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The anticancer immune response: indispensable for therapeutic success?
Laurence Zitvogel,Lionel Apetoh,François Ghiringhelli,Fabrice Andre,Antoine Tesniere,Guido Kroemer +5 more
TL;DR: This Review addresses the question, How may it be possible to ameliorate conventional therapies by stimulating the anticancer immune response and discusses the rationale of clinical trials to evaluate and eventually increase the contribution of antitumor immune responses to the therapeutic management of neoplasia.
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