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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 | Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study显示文摘 | Jean-Fran?ois Bosset Gilles Calais Laurent Mineur Philippe Maingon Suzana Stojanovic-Rundic René-Jean Bensadoun Etienne Bardet Alexander Beny Jean-Claude Ollier Michel Bolla Dominique Marchal Jean-Luc Van Laethem Vincent Klein Jordi Giralt Pierre Clavère | 2014 | Lancet Oncology2014，，2： | 2 |
| 3 | Selective requirement of PI3K/PDK1 signaling for Kras oncogene-driven pancreatic cell plasticity and cancer显示文摘 | Stefan Eser Nina Reiff Marlena Messer Barbara Seidler Kathleen Gottschalk Melanie Dobler Maren Hieber Andreas Arbeiter Sabine Klein Bo Kong Christoph W. Michalski Anna Melissa Schlitter Irene Esposito Alexander J. Kind Lena Rad Angelika E. Schnieke Manuel | 2013 | Cancer Cell2013，，： | 2 |
| 4 | The relevance of adjuvant therapy in primary carcinoma of the Fallopian tube, Stages I and II: Irradiation vs. chemotherapy显示文摘 | Matthias Klein Alexander Rosen Manfred Lahousen Anton-Helmut Graf Angelika Rainer | 2000 | International Journal of Radiation Oncology, Biology, Physics2000，，： | 1 |
| 5 | Heterotrophic nitrification in an acid forest soil and by an acid-tolerant fungus显示文摘 | STROO H F KLEIN T M M ALEXANDER | 1986 | Appl Environ Microbiol1986，52，： | 1 |
| 6 | Ambulance personnel and criti cal incidents: impact of accident and emergency work oL mental health and emotional well-being显示文摘 | Alexander D A Klein S | 2001 | Br J Psycbia try2001，178，1： | 1 |
| 7 | Fairness and contract design显示文摘 | Fehr Ernst Alexander Klein and Klaus M Schmidt | 2007 | Econometrica2007，75，1： | 1 |
| 8 | Vital Signs: Carbapenem-Resistant Enterobacteriaceae显示文摘 | Jacob Jesse T Klein Eili Laxminarayan Ramanan Beldavs Zintars Lynfield Ruth Kallen Alexander J Ricks Philip Edwards Jonathan Srinivasan Arjun Fridkin Scott Rasheed J Kamile Lonsway David Bulens Sandie Herrera Rosa McDonald L Clifford Patel | 2013 | MMWR Morbidity and Mortality Weekly Report2013，，9： | 1 |
| 9 | Ambulance personnel critical incidents:impact of Accident and emergency work on mental health and emotional well-being显示文摘 | Alexander DA Klein S | 2001 | Br J Psychiatry2001，178，1： | 1 |
| 10 | Ambulance personnel and critical inci- dents:impact of accident and emergency work on mental health and emotional well-being显示文摘 | Alexander DA Klein S | 2001 | Br J Psychiatry2001，178，1： | 1 |
| 11 | Ambulance personnel and critical incidents:Impact of accident and emergency work on mental health and emotional well - being显示文摘 | Alexander DA Klein S | 2001 | Br J Psychiatry2001，178，： | 1 |
| 12 | Biochemical terrorism : too awful to con- template, too serious to ignore : subjective literature review 显示文摘 | Alexander D A Klein S | 2003 | Br J Psychiatry2003，183，： | 1 |
| 13 | Pair-copula constructions for non-Gaussian DAG models显示文摘 | Alexander BAUER Claudia CZADO Thomas KLEIN | | 0，，01： | 1 |
| 14 | Insulin dependence and pancreatic enzyme replacement therapy are independent prognostic factors for long-term survival after operation for chronic pancreatitis显示文摘 | Markus Winny Vagia Paroglou Hüseyin Bektas Alexander Kaltenborn Benedikt Reichert Lea Zachau Moritz Kleine Jürgen Klempnauer Harald Schrem | 2013 | Surgery2013，，： | 1 |
| 15 | Gasification and pyrolysis显示文摘 | Alexander Klein Kevin Whiting Egan Archer | 2004 | Waste Manage World2004，，5： | 1 |
| 16 | Ambulance personnel and critical incidents : impact of accident and emergency work on mental health and emotional well - being 显示文摘 | Alexander DA Klein S | 2001 | J Br Psychiatry2001，178，1： | 1 |
| 17 | Ambulance personnel and critical in- cidents:impact of accident and emergency work on mental health and emotional well-being显示文摘 | Alexander DA Klein S | 2001 | Br J Psychiatry2001，178，1： | 1 |
| 18 | Infusion of CD133+ Bone Marrow–Derived Stem Cells After Selective Portal Vein Embolization Enhances Functional Hepatic Reserves After Extended Right Hepatectomy: A Retrospective Single-Center Study显示文摘 | Jan Schulte am Esch Moritz Schmelzle Günther Fürst Simon C. Robson Andreas Krieg Constanze Duhme Roy Y. Tustas Andrea Alexander Hans M. Klein Stefan A. Topp Johannes G. Bode Dieter H?ussinger Claus F. Eisenberger Wolfram Trudo Knoefel | 2012 | Annals of Surgery2012，，1： | 1 |
| 19 | Long-Term Results After Adult Ex Situ Split Liver Transplantation Since Its Introduction in 1987显示文摘 | Harald Schrem Moritz Kleine Tim Oliver Lankisch Alexander Kaltenborn Lampros Kousoulas Lea Zachau Frank Lehner Jürgen Klempnauer | 2014 | World Journal of Surgery2014，，7： | 1 |
| 20 | Recovery of arm function in patients with paresis after traumatic brain injury显示文摘 | Katz DI Alexander MP Klein RB | | 0，，： | 1 |
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