Newcastle disease virotherapy induces long-term survival and tumor-specific immune memory in orthotopic glioma through the induction of immunogenic cell death.
Carolien Koks,Abhishek D. Garg,Michael Ehrhardt,Matteo Riva,Lien Vandenberk,Louis Boon,Steven De Vleeschouwer,Patrizia Agostinis,Norbert Graf,Stefaan W. Van Gool +9 more
TLDR
The therapeutic activity of NDV against GL261 tumors, evidenced in an orthotopic mouse model, is described for the first time, and the importance of a functional adaptive immune system in this paradigm was demonstrated in immunodeficient Rag2−/− mice and in CD8+ T cell depleted animals, where NDV slightly prolonged survival, but failed to induce long‐term cure.Abstract:
The oncolytic features of several naturally oncolytic viruses have been shown on Glioblastoma Multiforme cell lines and in xenotransplant models. However, orthotopic glioma studies in immunocompetent animals are lacking. Here we investigated Newcastle disease virus (NDV) in the orthotopic, syngeneic murine GL261 model. Seven days after tumor induction, mice received NDV intratumorally. Treatment significantly prolonged median survival and 50% of animals showed long-term survival. We demonstrated immunogenic cell death (ICD) induction in GL261 cells after NDV infection, comprising calreticulin surface exposure, release of HMGB1 and increased PMEL17 cancer antigen expression. Uniquely, we found absence of secreted ATP. NDV-induced ICD occurred independently of caspase signaling and was blocked by Necrostatin-1, suggesting the contribution of necroptosis. Autophagy induction following NDV infection of GL261 cells was demonstrated as well. In vivo, elevated infiltration of IFN-γ(+) T cells was observed in NDV-treated tumors, along with reduced accumulation of myeloid derived suppressor cells. The importance of a functional adaptive immune system in this paradigm was demonstrated in immunodeficient Rag2(-/-) mice and in CD8(+) T cell depleted animals, where NDV slightly prolonged survival, but failed to induce long-term cure. Secondary tumor induction with GL261 cells or LLC cells in mice surviving long-term after NDV treatment, demonstrated the induction of a long-term, tumor-specific immunological memory response by ND virotherapy. For the first time, we describe the therapeutic activity of NDV against GL261 tumors, evidenced in an orthotopic mouse model. The therapeutic effect relies on the induction of ICD in the tumor cells, which primes adaptive antitumor immunity.read more
Citations
More filters
Journal ArticleDOI
From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review)
TL;DR: The present review focused on immunotherapy, with the aim of reducing side effects and increasing long-lasting efficacy in cancer therapy.
Journal ArticleDOI
Consensus guidelines for the definition, detection and interpretation of immunogenic cell death
Lorenzo Galluzzi,Ilio Vitale,Sarah Warren,Sandy Adjemian,Patrizia Agostinis,Aitziber Burque Martinez,Timothy A. Chan,George Coukos,Sandra Demaria,Eric Deutsch,Dobrin Draganov,Richard L. Edelson,Silvia C. Formenti,Jitka Fucikova,Lucia Gabriele,Udo S. Gaipl,Sofia R. Gameiro,Abhishek D. Garg,Encouse B. Golden,Jian Han,Kevin J. Harrington,Kevin J. Harrington,Akseli Hemminki,James W. Hodge,Dewan Md Sakib Hossain,Timothy M Illidge,Michael Karin,Howard L. Kaufman,Oliver Kepp,Guido Kroemer,Juan José Lasarte,Sherene Loi,Michael T. Lotze,Gwenola Manic,Taha Merghoub,Taha Merghoub,Alan Melcher,Karen L. Mossman,Felipe Prosper,Øystein Rekdal,Maria Rescigno,Chiara Riganti,Antonella Sistigu,Mark J. Smyth,Radek Spisek,John Stagg,Bryan E. Strauss,Daolin Tang,Kazuki Tatsuno,Stefaan Van Gool,Peter Vandenabeele,Takahiro Yamazaki,Dmitriy Zamarin,Dmitriy Zamarin,Laurence Zitvogel,Alessandra Cesano,Francesco M. Marincola +56 more
TL;DR: An updated operational definition of immunogenic cell death is provided, the key factors that dictate the ability of dying cells to drive an adaptive immune response are discussed, and experimental assays that are currently available for the assessment of ICD in vitro and in vivo are summarized.
Journal ArticleDOI
Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors.
TL;DR: Immunostimulatory chemotherapeutics stand out as promising partners for combination regimens involving immune checkpoint inhibitors, although additional research is required to identify the optimal regimens.
Journal ArticleDOI
The role of necroptosis in cancer biology and therapy
Yitao Gong,Zhiyao Fan,Guopei Luo,Chao Yang,Qiuyi Huang,Kun Fan,He Cheng,Kaizhou Jin,Quanxing Ni,Xianjun Yu,Chen Liu +10 more
TL;DR: The intricate role of necroptosis in tumor progression, cancer metastasis, prognosis of cancer patients, cancer immunity regulation, cancer subtype determination and cancer therapeutics is summarized.
Journal ArticleDOI
Necroptosis: Mechanisms and Relevance to Disease
TL;DR: Accumulating evidence indicates that necroptosis-deficient cancer cells are poorly immunogenic and hence escape natural and therapy-elicited immunosurveillance.
References
More filters
Journal ArticleDOI
The 2007 WHO Classification of Tumours of the Central Nervous System
David N. Louis,Hiroko Ohgaki,Otmar D. Wiestler,Webster K. Cavenee,Peter C. Burger,Anne Jouvet,Bernd W. Scheithauer,Paul Kleihues +7 more
TL;DR: The fourth edition of the World Health Organization (WHO) classification of tumours of the central nervous system, published in 2007, lists several new entities, including angiocentric glioma, papillary glioneuronal tumour, rosette-forming glioneurs tumour of the fourth ventricle, Papillary tumourof the pineal region, pituicytoma and spindle cell oncocytoma of the adenohypophysis.
Journal ArticleDOI
Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial
Roger Stupp,Monika E. Hegi,Warren P. Mason,Martin J. van den Bent,Martin J.B. Taphoorn,Robert C. Janzer,Samuel K. Ludwin,Anouk Allgeier,Barbara Fisher,Karl Belanger,Peter Hau,Alba A. Brandes,J.M.M. Gijtenbeek,Christine Marosi,Charles J. Vecht,Karima Mokhtari,Pieter Wesseling,Salvador Villà,Elizabeth Eisenhauer,Thierry Gorlia,Michael Weller,Denis Lacombe,J. Gregory Cairncross,René-Olivier Mirimanoff +23 more
TL;DR: Benefits of adjuvant temozolomide with radiotherapy lasted throughout 5 years of follow-up, and a benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years.
Journal ArticleDOI
Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial.
Walter Stummer,Uwe Pichlmeier,Thomas Meinel,Otmar D. Wiestler,Friedhelm E. Zanella,Hans-Jürgen Reulen +5 more
TL;DR: Tumour fluorescence derived from 5-aminolevulinic acid enables more complete resections of contrast-enhancing tumour, leading to improved progression-free survival in patients with malignant glioma.
Journal ArticleDOI
Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy.
Lionel Apetoh,François Ghiringhelli,Antoine Tesniere,Antoine Tesniere,Antoine Tesniere,Michel Obeid,Michel Obeid,Michel Obeid,Carla Ortiz,Carla Ortiz,Carla Ortiz,Alfredo Criollo,Alfredo Criollo,Alfredo Criollo,Grégoire Mignot,Grégoire Mignot,Grégoire Mignot,M. Chiara Maiuri,Evelyn Ullrich,Evelyn Ullrich,Evelyn Ullrich,Patrick Saulnier,Huan Yang,Sebastian Amigorena,Bernard Ryffel,Franck J. Barrat,Paul Saftig,Francis Lévi,Francis Lévi,Rosette Lidereau,Catherine Noguès,Jean-Paul Mira,Agnès Chompret,Virginie Joulin,Françoise Clavel-Chapelon,Jean Bourhis,Fabrice Andre,Suzette Delaloge,T. Tursz,Guido Kroemer,Guido Kroemer,Guido Kroemer,Laurence Zitvogel +42 more
TL;DR: A previously unrecognized pathway for the activation of tumor antigen–specific T-cell immunity that involves secretion of the high-mobility-group box 1 (HMGB1) alarmin protein by dying tumor cells and the action of HMGB1 on Toll-like receptor 4 (TLR4) expressed by dendritic cells (DCs) is described.
Journal ArticleDOI
Immunogenic Cell Death in Cancer Therapy
TL;DR: It is postulate that ICD constitutes a prominent pathway for the activation of the immune system against cancer, which in turn determines the long-term success of anticancer therapies and its subversion by pathogens.
Related Papers (5)
Calreticulin exposure dictates the immunogenicity of cancer cell death
Michel Obeid,Antoine Tesniere,Antoine Tesniere,Antoine Tesniere,François Ghiringhelli,François Ghiringhelli,François Ghiringhelli,Gian Maria Fimia,Lionel Apetoh,Lionel Apetoh,Lionel Apetoh,Jean-Luc Perfettini,Jean-Luc Perfettini,Jean-Luc Perfettini,Maria Castedo,Maria Castedo,Maria Castedo,Grégoire Mignot,Grégoire Mignot,Grégoire Mignot,Theoharis Panaretakis,Theoharis Panaretakis,Theoharis Panaretakis,Noelia Casares,Noelia Casares,Noelia Casares,Didier Métivier,Didier Métivier,Didier Métivier,Nathanael Larochette,Nathanael Larochette,Nathanael Larochette,Peter van Endert,Peter van Endert,Fabiola Ciccosanti,Mauro Piacentini,Laurence Zitvogel,Laurence Zitvogel,Laurence Zitvogel,Guido Kroemer,Guido Kroemer,Guido Kroemer +41 more
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
Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death.
Noelia Casares,Marie O. Pequignot,Antoine Tesniere,François Ghiringhelli,Stephan Roux,Nathalie Chaput,Elise Schmitt,Ahmed Hamaï,Sandra Hervas-Stubbs,Michel Obeid,Fréderic Philippe Coutant,Didier Métivier,Evelyne Pichard,Pierre Aucouturier,Gérard Pierron,Carmen Garrido,Laurence Zitvogel,Guido Kroemer +17 more