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| 1 | Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25显示文摘堵住抗体 ipilimumab 的细胞毒素的 T 淋巴细胞 antigen-4 (CTLA-4 ) 在很少的病人导致变形黑瘤的调停免疫者的长期的控制。尽管 ipilimumab 无疑经由 immunostimulation 施加它的治疗学的效果,这样远的临床上有用的、 immunologically 相关的 biomarkers 预言治疗效率是逃犯的。这里,我们显示出 IL-2 的那中立化或堵住 α并且 βIL-2 受体的子单元(CD25 和 CD122,分别地) 否则在现出症状之前的潜的老鼠模型由 CTLA-4 封锁导致了,废除了 antitumor 效果和 intratumoral T 受动器对规章的房间(Tregs ) 的比率的伴随的改进,它是。CTLA-4 封锁导致了在失去了 FoxP3 表示并且在 regressing 肿瘤积累了的 IL-2-producing 受动器房间与伴随物上升表示 Lag3, ICOS, IL-10 和 Egr2 的一个镇压 CD4 + T 房间子集的减小。当 recombinant IL-2 改进了 CTLA-4 封锁的治疗学的功效时,圈套 IL-2 受体 α(IL-2Rα, sCD25 ) 禁止了 CTLA-4 的 anticancer 效果封锁。在收到 ipilimumab 的 262 个变形黑瘤病人, sCD25 的基线浆液集中代表了全面幸存的独立指示物,与预言到治疗的抵抗的高水平。总的来说,这些结果解开为在 CTLA-4 的 anticancer 活动的 IL-2 和 IL-2 受体的一个角色封锁。重要地,我们的学习提供第一 immunologically 相关的 biomarker,也就是提高的浆液 sCD25,那与黑瘤在病人预言抵抗到 CTLA-4 封锁。 | Dalil Hannani Marie Vetizou David Enot Sylvie Rusakiewicz Nathalie Chaput David Klatzmann Melanie Desbois Nicolas Jacquelot Nadege Vimond Salem Chouaib Christine Mateus James P Allison Antoni Ribas Jedd D Wolchok Jianda Yuan Philip Wong Michael Postow Andrzej Mackiewicz Jacek Mackiewicz Dirk Schadendorff Dirk Jaeger Alan J Korman Keith Bahjat Michele Maio Luana Calabro Michele WL Teng Mark J Smyth Alexander Eggennont Caroline Robert Guido Kroemer Laurence Zitvogel | 2015 | Cell Research2015，25，2： | 14 |
| 2 | 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 |
| 3 | Inosine: novel microbiota-derived immunostimulatory metabolite显示文摘In a recent paper published in Science,Mager et al.identify inosine as a metabolite produced by Bifidobacterium pseudolongum that improves the efficacy of anticancer immunotherapy in mice.Inosine produced in the gut reaches adenosine A2A receptors of T lymphocytes infiltrating tumors;thus,inosine joins an expanding list of immunostimulatory metabolites produced in the gut. | Guido Kroemer Laurence Zitvogel | 2020 | Cell Research2020，30，11： | 4 |
| 4 | The role of the microbiota in inflammation, carcinogenesis, and cancer therapy显示文摘 | Amiran Dzutsev Romina S. Goldszmid Sophie Viaud Laurence Zitvogel Giorgio Trinchieri | 2015 | Eur. J. Immunol2015，，1： | 2 |
| 5 | Immunogenic Cell Death in Cancer Therapy显示文摘 | Guido Kroemer Lorenzo Galluzzi Oliver Kepp Laurence Zitvogel | 2013 | Annual Review of Immunology2013，，： | 2 |
| 6 | Mechanism of Action of Conventional and Targeted Anticancer Therapies: Reinstating Immunosurveillance显示文摘 | Laurence Zitvogel Lorenzo Galluzzi Mark J. Smyth Guido Kroemer | 2013 | Immunity2013，，1： | 2 |
| 7 | Interferon-γ induces cancer cell ferroptosis显示文摘Ferroptosis is an atypical cell death modality involving the oxidative destruction of cellular membranes following the failure of a glutathione-dependent antioxidant system.A recent paper by Wang et al. demonstrates that interferon-y prcxiuced by tumor-infiltrating T cells can kill cancer cells through the induction of ferroptosis. Cancers only develop if they escape from immunosurveillanee, and cancer therapies are successful when they succeed in rein stating the immune control of neoplastic lesi on s.1,2 This applies to all modalities of tumor treatments including chemotherapy. | Laurence Zitvogel Guido Kroemer | 2019 | Cell Research2019，29，9： | 2 |
| 8 | Immunogenic and tolerogenic cell death显示文摘 | Green D R Ferguson T Zitvogel L A | 2009 | Nat Rev Immunol2009，9，5： | 1 |
| 9 | Neutralizing tumor - promo-ting chronic inflammation: a magic bullet显示文摘 | CoussensL M Zitvogel L | 2013 | Science2013，339，6117： | 1 |
| 10 | Antigen presentation and T cell stimulation by dendritic cells显示文摘 | Guermonprez P Valladeau J Zitvogel L | 2002 | Annu Rev Immunol2002，20，： | 1 |
| 11 | Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes 显示文摘 | Zitvogel L Regnauh A Lozier A | 1998 | Nat Med1998，4，5： | 1 |
| 12 | Enhancement of antitumor immunity by expression of CD70 (CD27 ligand) or CD154 (CD40 ligand) costimulatory molecules in tumor cells显示文摘 | Couderc B Zitvogel L Douin-Echinard V | 1998 | Cancer Gene Ther1998，5，3： | 1 |
| 13 | Therapy of murine tumors with tumor peptide-pulsed dendritic cells :dependence on T cells,B7costimulation, and T helper cell 1 associated cytokines显示文摘 | ZITVOGEL L MAYORDOMO J I TJANDRAWAN T | 1996 | Exp Med1996，183，1： | 1 |
| 14 | Exosomes: composi- tion, biogenesis and function显示文摘 | Thery C Zitvogel L Amigorena S | 2002 | Nat Rev Immunol2002，2，8： | 1 |
| 15 | Autophagy and cellular immune responses显示文摘 | Ma Y Galluzzi L Zitvogel L | 2013 | Immunity2013，39，2： | 1 |
| 16 | Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients显示文摘 | Fran?ois Ghiringhelli Cedric Menard Pierre Emmanuel Puig Sylvain Ladoire Stephan Roux Fran?ois Martin Eric Solary Axel Le Cesne Laurence Zitvogel Bruno Chauffert | 2007 | Cancer Immunology Immunotherapy2007，，5： | 1 |
| 17 | Inflammasomes in carcinogenesis and anticancer immune responses 显示文摘 | Zitvogel L Kepp O Galluzzi L | 2012 | Nat Immunol2012，13，4： | 1 |
| 18 | Targeting PD-1/PD-L1 interactions for cancer immunotherapy显示文摘 | Laurence Zitvogel Guido Kroemer | 2012 | OncoImmunology2012，，8： | 1 |
| 19 | The secret ally:immu- nostimulation by anticancer drugs 显示文摘 | Galluzzi L Senovilla L Zitvogel L | 2012 | Nat Rev Drug Discov2012，11，3： | 1 |
| 20 | Exosomes:composition,biogenesis and function显示文摘 | Th6ry C Zitvogel L Amigorena S | 2002 | Nat Rev Immunol2002，2，8： | 1 |
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