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| 1 | Sustained Type I interferon signaling as a mechanism of resistance to PD-1 blockade显示文摘PD-1 blockade represents a major therapeutic avenue in anticancer immunotherapy.Delineating mechanisms of secondary resistance to this strategy is increasingly important.Here,we identified the deleterious role of signaling via the type I interferon(IFN)receptor in tumor and antigen presenting cells,that induced the expression of nitric oxide synthase 2(N0S2),associated with intratumor accumulation of regulatory T cells(Treg)and myeloid cells and acquired resistance to anti-PD-1 monoclonal antibody(mAb).Sustained IFNP transcription was observed in resistant tumors,in turn inducing PD-L1 and N0S2 expression in both tumor and dendritic cells(DC).Whereas PD-L1 was not involved in secondary resistance to anti-PD-1 mAb,pharmacological or genetic inhibition of N0S2 maintained long-term control of tumors by PD-1 blockade,through reduction of Treg and DC activation.Resistance to immunotherapies,including anti-PD-1 mAb in melanoma patients,was also correlated with the induction of a type I IFN signature.Hence,the role of type I IFN in response to PD-1 blockade should be revisited as sustained type I IFN signaling may contribute to resistance to therapy. | Nicolas Jacquelot Takahiro Yamazaki Maria PRoberti Connie PMDuong Miles CAndrews Loic Verlingue Gladys Ferrere Sonia Becharef Marie Vetizou Romain Daillere Meriem Messaoudene David PEnot Gautier Stoll Stefano Ugel Maria Marigo Shin Foong Ngiow Aurelien Marabelle Armelle Prevost-Blondel Pierre-Olivier Gaudreau Vancheswaran Gopalakrishnan Alexander MEggermont Paule Opolon Christophe Klein Gabriele Madonna Paolo AAscierto Antje Sucker Dirk Schadendorf Mark JSm yth Jean-Charles Soria Guido Kroemer Vincenzo Bronte Jennifer Wargo and Laurence Zitvogel | 2019 | Cell Research2019，29，10： | 6 |
| 2 | Macrophage immunomodulatory activity of polysaccharides isolated from Opuntia polyacantha显示文摘 | Igor A. Schepetkin Gang Xie Liliya N. Kirpotina Robyn A. Klein Mark A. Jutila Mark T. Quinn | 2008 | International Immunopharmacology2008，，10： | 2 |
| 3 | Frequent Detection of Pancreatic Lesions in Asymptomatic High-Risk Individuals显示文摘 | Marcia Irene Canto Ralph H. Hruban Elliot K. Fishman Ihab R. Kamel Richard Schulick Zhe Zhang Mark Topazian Naoki Takahashi Joel Fletcher Gloria Petersen Alison P. Klein Jennifer Axilbund Constance Griffin Sapna Syngal John R. Saltzman Koenraad J. Mortele | 2012 | Gastroenterology2012，，4： | 2 |
| 4 | miR-181a Is an Intrinsic Modulator of T Cell Sensitivity and Selection显示文摘 | Qi-Jing Li Jacqueline Chau Peter J.R. Ebert Giselle Sylvester Hyeyoung Min Gwen Liu Ravi Braich Muthiah Manoharan Juergen Soutschek Petra Skare Lawrence O. Klein Mark M. Davis Chang-Zheng Chen | 2007 | Cell2007，，1： | 2 |
| 5 | A MACHINE LEARNING APPROACH FOR MECHANISM SELECTION IN COMPLEX NEGOTIATIONS显示文摘 | Reyhan Aydogan Ivan Marsa-Maestre Mark Klein Catholijn M. Jonker | 2018 | Journal of Systems Science and Systems Engineering2018，27，2： | 2 |
| 6 | miR-181a Is an Intrinsic Modulator of T Cell Sensitivity and Selection显示文摘 | Qi-Jing Li Jacqueline Chau Peter J.R. Ebert Giselle Sylvester Hyeyoung Min Gwen Liu Ravi Braich Muthiah Manoharan Juergen Soutschek Petra Skare Lawrence O. Klein Mark M. Davis Chang-Zheng Chen | 2007 | Cell2007，，1： | 1 |
| 7 | Frequent Detection of Pancreatic Lesions in Asymptomatic High-Risk Individuals显示文摘 | Marcia Irene Canto Ralph H. Hruban Elliot K. Fishman Ihab R. Kamel Richard Schulick Zhe Zhang Mark Topazian Naoki Takahashi Joel Fletcher Gloria Petersen Alison P. Klein Jennifer Axilbund Constance Griffin Sapna Syngal John R. Saltzman Koenraad J. Mortele | 2012 | Gastroenterology2012，，4： | 1 |
| 8 | c-Met Confers Protection Against Chronic Liver Tissue Damage and Fibrosis Progression After Bile Duct Ligation in Mice显示文摘 | Arne Giebeler Mark V. Boekschoten Christian Klein Malgorzata Borowiak Carmen Birchmeier Nikolaus Gassler Hermann E. Wasmuth Michael Müller Christian Trautwein Konrad L. Streetz | 2009 | Gastroenterology2009，，1： | 1 |
| 9 | Empagliflozin, a no- vel potem and selective SGLT-2 inhibitior, improves glycaemic control alone and in combination with insulin in streptozotocin-in- duced diabetic rats, a model of type 1 disabetes mellitus 显示文摘 | LUIPPOLD G KLEIN T MARK M | 2012 | Di- abets Obes Metab2012，14，7： | 1 |
| 10 | Inappropriate Implantable Cardioverter-Defibrillator Shocks in MADIT II显示文摘 | James P. Daubert Wojciech Zareba David S. Cannom Scott McNitt Spencer Z. Rosero Paul Wang Claudio Schuger Jonathan S. Steinberg Steven L. Higgins David J. Wilber Helmut Klein Mark L. Andrews W. Jackson Hall Arthur J. Moss | 2008 | Journal of the American College of Cardiology2008，，14： | 1 |
| 11 | Modelling collective decision making in groups and crowds: Integrating social contagion and interacting emotions, beliefs and intentions显示文摘 | Tibor Bosse Mark Hoogendoorn Michel C. A. Klein Jan Treur C. Natalie Wal Arlette Wissen | 2013 | Autonomous Agents and Multi-Agent Systems2013，，1： | 1 |
| 12 | Knowledge discovery in time series databases 显示文摘 | MARK L KLEIN Y KANDEL A | 2001 | IEEE Transactions on Systems Man and Cybernetics2001，31，1： | 1 |
| 13 | Evidence and Implications of Recent Climate Change in Northern Alaska and Other Arctic Regions显示文摘 | Larry D. Hinzman Neil D. Bettez W. Robert Bolton F. Stuart Chapin Mark B. Dyurgerov Chris L. Fastie Brad Griffith Robert D. Hollister Allen Hope Henry P. Huntington Anne M. Jensen Gensuo J. Jia Torre Jorgenson Douglas L. Kane David R. Klein Gary Kofinas A | 2005 | Climatic Change2005，，3： | 1 |
| 14 | Cognitive-Behavioral Therapy for Adolescent Depression: A Meta-Analytic Investigation of Changes in Effect-Size Estimates显示文摘 | JESSE B. KLEIN RACHEL H. JACOBS MARK A. REINECKE | 2007 | Journal of the American Academy of Child & Adolescent Psychiatry2007，，11： | 1 |
| 15 | Evidence and Implications of Recent Climate Change in Northern Alaska and Other Arctic Regions显示文摘 | Larry D. Hinzman Neil D. Bettez W. Robert Bolton F. Stuart Chapin Mark B. Dyurgerov Chris L. Fastie Brad Griffith Robert D. Hollister Allen Hope Henry P. Huntington Anne M. Jensen Gensuo J. Jia Torre Jorgenson Douglas L. Kane David R. Klein Gary Kofinas A | 2005 | Climatic Change2005，，3： | 1 |
| 16 | c-Met Confers Protection Against Chronic Liver Tissue Damage and Fibrosis Progression After Bile Duct Ligation in Mice显示文摘 | Arne Giebeler Mark V. Boekschoten Christian Klein Malgorzata Borowiak Carmen Birchmeier Nikolaus Gassler Hermann E. Wasmuth Michael Müller Christian Trautwein Konrad L. Streetz | 2009 | Gastroenterology2009，，1： | 1 |
| 17 | C/T polymorphism of the intercellular adhesion molecule-1 gene (exon 6, codon 469). A risk factor for coronary heart disease and myocardial infarction显示文摘 | Hong Jiang Rolf Michael Klein Dieter Niederacher Ming Du Roger Marx Mark Horlitz Guido Boerrigter Harald Lapp Thomas Scheffold Ingo Krakau Hartmut Gülker | 2002 | International Journal of Cardiology2002，，2： | 1 |
| 18 | Supporting conflict resolution in cooperative design systems显示文摘 | Mark Klein | 1991 | IEEE Transactions on Systems Man and Cybernetics1991，21，6： | 1 |
| 19 | Supporting conflict resolution in cooperative design system 显示文摘 | Mark Klein | 1991 | IEEE Transactions on Systems Man and Cybernetics1991，21，6： | 1 |
| 20 | Evidence and Implications of Recent Climate Change in Northern Alaska and Other Arctic Regions显示文摘 | Larry D. Hinzman Neil D. Bettez W. Robert Bolton F. Stuart Chapin Mark B. Dyurgerov Chris L. Fastie Brad Griffith Robert D. Hollister Allen Hope Henry P. Huntington Anne M. Jensen Gensuo J. Jia Torre Jorgenson Douglas L. Kane David R. Klein Gary Kofinas A | 2005 | Climatic Change2005，，3： | 1 |
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