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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 | Natural history of liver fibrosis progression in patients with chronic hepatitis C显示文摘 | Thierry Poynard Pierre Bedossa Pierre Opolon | 1997 | The Lancet . 1997 (9055)1997，，： | 3 |
| 3 | Combined effects of docetaxel and angiostatin gene therapy in prostate tumor model显示文摘 | GALAUP A OPOLON P BOUQUET C | 2003 | Mol Ther2003，7，6： | 1 |
| 4 | New potential and applications of contrast-enhanced ultrasound of the breast:Own investigations and review of the literature显示文摘 | Balleyguier C Opolon P Mathieu M C | 2009 | Eur J Radiol2009，69，1： | 1 |
| 5 | Adenovirus-mediated transfer of the thyroid sodium/iodide symporter gene into tumors for a targeted radiotherapy显示文摘 | Boland A Ricard M Opolon P | 2000 | Cancer Res2000，60，13： | 1 |
| 6 | New potential and applications of contrast-enhanced ultrasound of the breast: Own investigations and review of the literature显示文摘 | Balleyguier C Opolon P Mathieu MC | 2009 | Eur J Radiol2009，69，1： | 1 |
| 7 | High vaccination efficiency of low-affinity epitopes in antitumor immunotherapy 显示文摘 | Gross D A Graff Dubois S Opolon P | 2004 | J Clin Invest2004，113，3： | 1 |
| 8 | New potential and applications of contrast-enhanced ultrasound of the breast: own investigations and review of the literature 显示文摘 | Balleyguier C Opolon P Mathieu MC | 2009 | Eur J Radiol2009，69，1： | 1 |
| 9 | New potential and applications of contrast-enhanced ultrasound of the breast:own investigations and review of the literature显示文摘 | Balleyguier C Opolon P Mathieu MC | 2009 | Eur J Radiol2009，69，1： | 1 |
| 10 | Adenovirus-mediated transfer of the sodium/iodide symporter gene into tumors for a targeted radio-therapy显示文摘 | Ricard M Opolon P | 2000 | Cancer Res2000，60，： | 1 |
| 11 | Antibiotic prophylaxis (AbP) for the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding (GB):A meta-analysis显示文摘 | Bernard B Nguyen KE Opolon P Poynard T | | 0，，： | 1 |
| 12 | Expression of p53,or targeting towards EGFR,enhances the oncolytic potency of conditionally replicative adenovirus against neuroblastoma显示文摘 | Geoerger B van Beusechem VW Opolon P | 2005 | J Gene Med2005，7，5： | 1 |
| 13 | Adenovirus-mediated gene transfer to the transplanted piglet heart after intracoronary injection显示文摘 | Griscelli F Belli E Opolon P | 2003 | J Gene Med2003，5，2： | 1 |
| 14 | Natural history of liver fibrosis progression in patients with chronic hepatitis C显示文摘 | Poynard T Bedossa P Opolon P | 1997 | Lancet1997，349，9055： | 1 |
| 15 | Expression of p53,or targeting towards EGFR,enhances the oncolytic potency of conditionally replicative adenovirus against neuroblastoma显示文摘 | Geoerger B van Beusechem VW Opolon P | | 0，，5： | 1 |
| 16 | Oncolytic activity of the E1B-55 kDa-deleted adenovirus ONYX-015 is independent of cellular p53 status in human malignant glioma xenografts显示文摘 | Geoerger B Grill J Opolon P | 2002 | Cancer Res2002，62，3： | 1 |
| 17 | Arsenic trioxide: a promising novel therapeu- tic agent for lymphoproliferative and autoimmune syn- dromes in MRL/lpr mice显示文摘 | Bob6 P Bonardelle D Benihoud K Opolon P Chelbi- Alix MK | 2006 | Blood2006，108，13： | 1 |
| 18 | Propranolol and sclerotherapy in the prevention of gastrointestinal rebleeding in patients with cirrhosis: a meta-analysis显示文摘 | Brigitte Bernard Didier Lebrec Philippe Mathurin Pierre Opolon Thierry Poynard | 1997 | Journal of Hepatology1997，，2： | 1 |
| 19 | Adenovirus-mediated transfer of the thyroid sodium/iodide symporter gene into tumors for a targeted radiotherapy显示文摘 | Boland A Ricard M Opolon P | 2000 | Cancer Res2000，60，13： | 1 |
| 20 | Hepatic failure coma treated by poluacrylonitrile membrance bemodialysis显示文摘 | Opolon P Rapin JR Huguet C | 1976 | Trans Am Soc Artif Intern Organs1976，22，： | 1 |
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