Unleashing the power of immune checkpoints: Post-translational modification of novel molecules and clinical applications.
暂无分享,去创建一个
Xianjie Jiang | Yian Wang | Jie Wang | Meifang Xu | Meifeng Wang | Rong Wang | Boshu Zheng | Mingfen Chen | Qi Ke | Jun Long
[1] Ni Hong,et al. Sirpα on tumor-associated myeloid cells restrains antitumor immunity in colorectal cancer independent of its interaction with CD47. , 2024, Nature cancer.
[2] N. Tang,et al. SUMOylation inhibitors activate anti-tumor immunity by reshaping the immune microenvironment in a preclinical model of hepatocellular carcinoma. , 2023, Cellular oncology.
[3] S. Gardai,et al. Nonfucosylation of an anti-TIGIT antibody enhances FcγR engagement, driving innate immune activation and antitumor activity , 2023, Frontiers in immunology.
[4] Z. Zeng,et al. CD155 and its receptors in cancer immune escape and immunotherapy. , 2023, Cancer letters.
[5] Xu Qian,et al. EGFR‐Induced and c‐Src‐Mediated CD47 Phosphorylation Inhibits TRIM21‐Dependent Polyubiquitylation and Degradation of CD47 to Promote Tumor Immune Evasion , 2023, Advanced science.
[6] Kun-Pin Wu,et al. SheddomeDB 2023: A Revision of an Ectodomain Shedding Database Based on a Comprehensive Literature Review and Online Resources , 2023, Journal of proteome research.
[7] M. Cippitelli,et al. SUMOylation and related post-translational modifications in natural killer cell anti-cancer responses , 2023, Frontiers in Cell and Developmental Biology.
[8] H. Tawbi,et al. The introduction of LAG-3 checkpoint blockade in melanoma: immunotherapy landscape beyond PD-1 and CTLA-4 inhibition , 2023, Therapeutic advances in medical oncology.
[9] Mingli Xiang,et al. B7 family protein glycosylation: Promising novel targets in tumor treatment , 2022, Frontiers in Immunology.
[10] Cheng Xu,et al. Checkpoint Nano‐PROTACs for Activatable Cancer Photo‐Immunotherapy , 2022, Advanced materials.
[11] J. Welsh,et al. Inhibition of the CD47-SIRPα axis for cancer therapy: A systematic review and meta-analysis of emerging clinical data , 2022, Frontiers in Immunology.
[12] Yajun Zhang,et al. Small-Molecule PROTACs for Cancer Immunotherapy , 2022, Molecules.
[13] Liang Chen,et al. Strategies for developing PD-1 inhibitors and future directions. , 2022, Biochemical pharmacology.
[14] M. Kiebish,et al. The Next Frontier: Translational Development of Ubiquitination, SUMOylation, and NEDDylation in Cancer , 2022, International journal of molecular sciences.
[15] Kristina Xega,et al. The SUMOylation inhibitor subasumstat potentiates rituximab activity by IFN1-dependent macrophage and NK cell stimulation , 2022, Blood.
[16] K. Wucherpfennig,et al. MICA/B-targeted antibody promotes NK cell–driven tumor immunity in patients with intrahepatic cholangiocarcinoma , 2022, Oncoimmunology.
[17] Xiaolong Yan,et al. Emerging role of ubiquitination/deubiquitination modification of PD-1/PD-L1 in cancer immunotherapy , 2022, Genes & diseases.
[18] J. Rip,et al. Targeting pancreatic cancer by TAK-981: a SUMOylation inhibitor that activates the immune system and blocks cancer cell cycle progression in a preclinical model , 2022, Gut.
[19] Anson Snow,et al. The development of pevonedistat in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML): hope or hype? , 2022, Therapeutic advances in hematology.
[20] C. Robert. LAG-3 and PD-1 blockade raises the bar for melanoma , 2021, Nature Cancer.
[21] A. Shibuya,et al. DNAM-1 versus TIGIT: competitive roles in tumor immunity and inflammatory responses. , 2021, International immunology.
[22] B. Helmink,et al. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade , 2021, Cell.
[23] Zhen Bian,et al. SIRPα sequesters SHP-2 to promote IL-4 and IL-13 signaling and the alternative activation of macrophages , 2021, Science Signaling.
[24] J. Wolchok,et al. Enhancing immunotherapy in cancer by targeting emerging immunomodulatory pathways , 2021, Nature Reviews Clinical Oncology.
[25] Steven S. Langston,et al. A small-molecule SUMOylation inhibitor activates antitumor immune responses and potentiates immune therapies in preclinical models , 2021, Science Translational Medicine.
[26] A. Santoni,et al. Immunomodulatory effect of NEDD8-activating enzyme inhibition in Multiple Myeloma: upregulation of NKG2D ligands and sensitization to Natural Killer cell recognition , 2021, Cell Death & Disease.
[27] Feng Xu,et al. Poliovirus receptor (PVR)-like protein cosignaling network: new opportunities for cancer immunotherapy , 2021, Journal of experimental & clinical cancer research : CR.
[28] K. Wucherpfennig,et al. MICA/B antibody induces macrophage-mediated immunity against acute myeloid leukemia. , 2021, Blood.
[29] M. Fuertes,et al. Leveraging NKG2D Ligands in Immuno-Oncology , 2021, Frontiers in Immunology.
[30] D. Wainwright,et al. Tumor-derived NKG2D ligand sMIC reprograms NK cells to an inflammatory phenotype through CBM signalosome activation , 2021, Communications biology.
[31] P. Trzonkowski,et al. KIR Receptors as Key Regulators of NK Cells Activity in Health and Disease , 2021, Cells.
[32] Y. Kikushige. TIM‐3 in normal and malignant hematopoiesis: Structure, function, and signaling pathways , 2021, Cancer science.
[33] J. Lohmueller,et al. The costimulatory activity of Tim-3 requires Akt and MAPK signaling and its recruitment to the immune synapse , 2021, Science Signaling.
[34] A. Regev,et al. TIM-3 restrains anti-tumour immunity by regulating inflammasome activation , 2021, Nature.
[35] Qian Wang,et al. Generation of TIM3 inhibitory single-domain antibodies to boost the antitumor activity of chimeric antigen receptor T cells , 2021, Oncology letters.
[36] T. Kaisho,et al. The inhibitory receptor TIM-3 limits activation of the cGAS-STING pathway in intra-tumoral dendritic cells by suppressing extracellular DNA uptake. , 2021, Immunity.
[37] F. Hodi,et al. Phase I/Ib Clinical Trial of Sabatolimab, an Anti–TIM-3 Antibody, Alone and in Combination with Spartalizumab, an Anti–PD-1 Antibody, in Advanced Solid Tumors , 2021, Clinical Cancer Research.
[38] A. Regev,et al. Tim-3 adaptor protein Bat3 is a molecular checkpoint of T cell terminal differentiation and exhaustion , 2021, Science Advances.
[39] Y. Lou,et al. Next generation of immune checkpoint inhibitors and beyond , 2021, Journal of Hematology & Oncology.
[40] H. Hang,et al. Protein S-palmitoylation in immunity , 2021, Open Biology.
[41] N. Vélez de Mendizábal,et al. Blocking TIM-3 in Treatment-refractory Advanced Solid Tumors: A Phase Ia/b Study of LY3321367 with or without an Anti-PD-L1 Antibody , 2021, Clinical Cancer Research.
[42] Jiaxin Liu,et al. Targeting the ubiquitination/deubiquitination process to regulate immune checkpoint pathways , 2021, Signal Transduction and Targeted Therapy.
[43] Lucas Ferrari de Andrade,et al. NKG2D and MICA/B shedding: a ‘tag game’ between NK cells and malignant cells , 2020, Clinical & translational immunology.
[44] F. He,et al. Neddylation of PTEN regulates its nuclear import and promotes tumor development , 2020, Cell Research.
[45] Domarin Khago,et al. The Role of Conformational Dynamics in the Recognition and Regulation of Ubiquitination , 2020, Molecules.
[46] K. Venkatakrishnan,et al. Phase I study assessing the mass balance, pharmacokinetics, and excretion of [14C]-pevonedistat, a NEDD8-activating enzyme inhibitor in patients with advanced solid tumors , 2020, Investigational New Drugs.
[47] Yoshiki Narimatsu,et al. Global view of human protein glycosylation pathways and functions , 2020, Nature Reviews Molecular Cell Biology.
[48] G. Kristiansen,et al. CD155 on Tumor Cells Drives Resistance to Immunotherapy by Inducing the Degradation of the Activating Receptor CD226 in CD8+ T Cells. , 2020, Immunity.
[49] M. Otsuka,et al. The fatty-acid amide hydrolase inhibitor URB597 inhibits MICA/B shedding , 2020, Scientific Reports.
[50] I. Bahar,et al. Pharmacological suppression of B7-H4 glycosylation restores antitumor immunity in immune-cold breast cancers. , 2020, Cancer discovery.
[51] T. Okazaki,et al. LAG-3: from molecular functions to clinical applications , 2020, Journal for ImmunoTherapy of Cancer.
[52] G. Lajoie,et al. ADAM protease inhibition overcomes resistance of breast cancer stem-like cells to γδ T cell immunotherapy , 2020, bioRxiv.
[53] K. Madauss,et al. Restoration of antitumor immunity through anti-MICA antibodies elicited with a chimeric protein , 2020, Journal for immunotherapy of cancer.
[54] J. Pruneda,et al. The Tumour Suppressor TMEM127 Is a Nedd4-Family E3 Ligase Adaptor Required by Salmonella SteD to Ubiquitinate and Degrade MHC Class II Molecules , 2020, Cell host & microbe.
[55] T. Schumacher,et al. The CD47-SIRPα Immune Checkpoint. , 2020, Immunity.
[56] Q. Jiang,et al. K6-linked SUMOylation of BAF regulates nuclear integrity and DNA replication in mammalian cells , 2020, Proceedings of the National Academy of Sciences.
[57] Wenyi Wei,et al. The role of ubiquitination in tumorigenesis and targeted drug discovery , 2020, Signal Transduction and Targeted Therapy.
[58] Lin Sun,et al. Recent Advances in Molecular Mechanisms of the NKG2D Pathway in Hepatocellular Carcinoma , 2020, Biomolecules.
[59] B. Schulman,et al. NEDD8 nucleates a multivalent cullin-RING-UBE2D ubiquitin ligation assembly , 2020, Nature.
[60] Xianqun Fan,et al. SUMOylation homeostasis in tumorigenesis. , 2019, Cancer letters.
[61] Kongming Wu,et al. Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4 , 2019, Molecular Cancer.
[62] Jia-Yu Wang,et al. B7-H4, a promising target for immunotherapy. , 2019, Cellular immunology.
[63] S. M. Toor,et al. Breast Cancer Cells and PD-1/PD-L1 Blockade Upregulate the Expression of PD-1, CTLA-4, TIM-3 and LAG-3 Immune Checkpoints in CD4+ T Cells , 2019, Vaccines.
[64] A. Gartner,et al. The Balance between Mono- and NEDD8-Chains Controlled by NEDP1 upon DNA Damage Is a Regulatory Module of the HSP70 ATPase Activity , 2019, Cell reports.
[65] Qiang Zhang,et al. Neddylation inhibition upregulates PD‐L1 expression and enhances the efficacy of immune checkpoint blockade in glioblastoma , 2019, International journal of cancer.
[66] J. Mintern,et al. MARCH ligases in immunity. , 2019, Current opinion in immunology.
[67] H. Puhr,et al. New emerging targets in cancer immunotherapy: the role of LAG3 , 2019, ESMO Open.
[68] Jean-David Fumet,et al. Tim-3/galectin-9 pathway and mMDSC control primary and secondary resistances to PD-1 blockade in lung cancer patients , 2019, Oncoimmunology.
[69] Z. Zeng,et al. Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape , 2019, Molecular Cancer.
[70] G. Zhu,et al. Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3 , 2019, Cell.
[71] M. Hung,et al. Posttranslational Modifications of PD-L1 and Their Applications in Cancer Therapy. , 2018, Cancer research.
[72] L. Macdonald,et al. Combination cancer immunotherapy targeting PD-1 and GITR can rescue CD8+ T cell dysfunction and maintain memory phenotype , 2018, Science Immunology.
[73] S. Dixon,et al. Protein palmitoylation and cancer , 2018, EMBO reports.
[74] B. Walcheck,et al. Anti-ADAM17 monoclonal antibody MEDI3622 increases IFNγ production by human NK cells in the presence of antibody-bound tumor cells , 2018, Cancer Immunology, Immunotherapy.
[75] D. Faller,et al. Phase Ib study of pevonedistat, a NEDD8-activating enzyme inhibitor, in combination with docetaxel, carboplatin and paclitaxel, or gemcitabine, in patients with advanced solid tumors , 2018, Investigational new drugs.
[76] D. Faller,et al. Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, combined with azacitidine in patients with AML. , 2018, Blood.
[77] H. Nishiura,et al. Inhibition of Asparagine-linked Glycosylation Participates in Hypoxia-induced Down-regulation of Cell-surface MICA Expression. , 2018, Anticancer research.
[78] Geoff S. Higgins,et al. Oxidative Phosphorylation as an Emerging Target in Cancer Therapy , 2018, Clinical Cancer Research.
[79] B. Shen,et al. Negative regulation of Nod‐like receptor protein 3 inflammasome activation by T cell Ig mucin‐3 protects against peritonitis , 2018, Immunology.
[80] V. de Turris,et al. Innate immune activating ligand SUMOylation affects tumor cell recognition by NK cells , 2017, Scientific Reports.
[81] Ana Magalhães,et al. Protein glycosylation in gastric and colorectal cancers: Toward cancer detection and targeted therapeutics. , 2017, Cancer letters.
[82] R. Kumar,et al. Phosphorylation: Implications in Cancer , 2017, The Protein Journal.
[83] K. Odunsi,et al. Compensatory upregulation of PD-1, LAG-3, and CTLA-4 limits the efficacy of single-agent checkpoint blockade in metastatic ovarian cancer , 2016, Oncoimmunology.
[84] N. L. La Gruta,et al. Ubiquitin ligase MARCH 8 cooperates with CD83 to control surface MHC II expression in thymic epithelium and CD4 T cell selection , 2016, The Journal of experimental medicine.
[85] Jian-nan Feng,et al. Tim-3 promotes tumor-promoting M2 macrophage polarization by binding to STAT1 and suppressing the STAT1-miR-155 signaling axis , 2016, Oncoimmunology.
[86] G. Freeman,et al. Coinhibitory Pathways in the B7-CD28 Ligand-Receptor Family. , 2016, Immunity.
[87] Shohei Koyama,et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints , 2016, Nature Communications.
[88] P. Lehner,et al. Identifying the ERAD ubiquitin E3 ligases for viral and cellular targeting of MHC class I , 2015, Molecular immunology.
[89] M. Colonna,et al. DNAM-1 controls NK cell activation via an ITT-like motif , 2015, The Journal of experimental medicine.
[90] A. Legat,et al. Vaccination with LAG-3Ig (IMP321) and Peptides Induces Specific CD4 and CD8 T-Cell Responses in Metastatic Melanoma Patients—Report of a Phase I/IIa Clinical Trial , 2015, Clinical Cancer Research.
[91] S. Pinho,et al. Glycosylation in cancer: mechanisms and clinical implications , 2015, Nature Reviews Cancer.
[92] Zihai Li,et al. Nonblocking Monoclonal Antibody Targeting Soluble MIC Revamps Endogenous Innate and Adaptive Antitumor Responses and Eliminates Primary and Metastatic Tumors , 2015, Clinical Cancer Research.
[93] M. Maris,et al. Pevonedistat (MLN4924), a First‐in‐Class NEDD8‐activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study , 2015, British journal of haematology.
[94] M. Weekes,et al. Plasma Membrane Profiling Defines an Expanded Class of Cell Surface Proteins Selectively Targeted for Degradation by HCMV US2 in Cooperation with UL141 , 2015, PLoS pathogens.
[95] M. Peter,et al. Protein neddylation: beyond cullin–RING ligases , 2014, Nature Reviews Molecular Cell Biology.
[96] J. Hackney,et al. The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function. , 2014, Cancer cell.
[97] Yibing Chen,et al. UPR decreases CD226 ligand CD155 expression and sensitivity to NK cell‐mediated cytotoxicity in hepatoma cells , 2014, European journal of immunology.
[98] Hidde L. Ploegh,et al. CEACAM1 regulates TIM-3-mediated tolerance and exhaustion , 2014, Nature.
[99] A. Santoni,et al. c‐Cbl regulates MICA‐ but not ULBP2‐induced NKG2D down‐modulation in human NK cells , 2014, European journal of immunology.
[100] P. Altevogt,et al. Metalloprotease-mediated tumor cell shedding of B7-H6, the ligand of the natural killer cell-activating receptor NKp30. , 2014, Cancer research.
[101] T. K. van den Berg,et al. The interaction between signal regulatory protein alpha (SIRPα) and CD47: structure, function, and therapeutic target. , 2014, Annual review of immunology.
[102] P. Sun,et al. Natural Killer Cell-Mediated Shedding of ULBP2 , 2014, PloS one.
[103] M. Weller,et al. A disintegrin and metalloproteinases 10 and 17 modulate the immunogenicity of glioblastoma-initiating cells. , 2014, Neuro-oncology.
[104] M. Ostrowski,et al. T Cell Ig and Mucin Domain–Containing Protein 3 Is Recruited to the Immune Synapse, Disrupts Stable Synapse Formation, and Associates with Receptor Phosphatases , 2014, The Journal of Immunology.
[105] J. Scheller,et al. A Disintegrin and Metalloprotease (ADAM) 10 and ADAM17 Are Major Sheddases of T Cell Immunoglobulin and Mucin Domain 3 (Tim-3)* , 2013, The Journal of Biological Chemistry.
[106] A. Santoni,et al. Inhibition of Glycogen Synthase Kinase-3 Increases NKG2D Ligand MICA Expression and Sensitivity to NK Cell–Mediated Cytotoxicity in Multiple Myeloma Cells: Role of STAT3 , 2013, The Journal of Immunology.
[107] S. Thorne,et al. Potential for Enhanced Therapeutic Activity of Biological Cancer Therapies with Doxycycline Combination , 2012, Gene Therapy.
[108] C. Li,et al. Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule polarization and cytotoxicity of NK cells , 2012, Cell Death and Differentiation.
[109] Sheng Xiao,et al. Bat3 promotes T cell responses and autoimmunity by repressing Tim-3–mediated cell death and exhaustion , 2012, Nature Medicine.
[110] H. Yoshiyama,et al. Tumor-infiltrating DCs suppress nucleic acid–mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1 , 2012, Nature Immunology.
[111] T. Kuroishi,et al. Histamine reduces susceptibility to natural killer cells via down‐regulation of NKG2D ligands on human monocytic leukaemia THP‐1 cells , 2012, Immunology.
[112] Michael Hagemann-Jensen,et al. 2-Deoxy d-Glucose Prevents Cell Surface Expression of NKG2D Ligands through Inhibition of N-Linked Glycosylation , 2012, The Journal of Immunology.
[113] T. Spies,et al. Expression of ERp5 and GRP78 on the membrane of chronic lymphocytic leukemia cells: association with soluble MICA shedding , 2012, Cancer Immunology, Immunotherapy.
[114] Eric O Long,et al. Palmitoylation of MICA, a ligand for NKG2D, mediates its recruitment to membrane microdomains and promotes its shedding , 2011, European journal of immunology.
[115] Jenna M. Sullivan,et al. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity , 2010, The Journal of experimental medicine.
[116] M. Gutiérrez,et al. First-line chemoimmunotherapy in metastatic breast carcinoma: combination of paclitaxel and IMP321 (LAG-3Ig) enhances immune responses and antitumor activity , 2010, Journal of Translational Medicine.
[117] A. Santoni,et al. Heat Shock Protein-90 Inhibitors Increase MHC Class I-Related Chain A and B Ligand Expression on Multiple Myeloma Cells and Their Ability to Trigger NK Cell Degranulation1 , 2009, The Journal of Immunology.
[118] B. Escudier,et al. A Phase I Pharmacokinetic and Biological Correlative Study of IMP321, a Novel MHC Class II Agonist, in Patients with Advanced Renal Cell Carcinoma , 2009, Clinical Cancer Research.
[119] Steven C Almo,et al. T cell immunoglobulin mucin-3 crystal structure reveals a galectin-9-independent ligand-binding surface. , 2007, Immunity.
[120] C. Blobel,et al. Metalloproteases regulate T‐cell proliferation and effector function via LAG‐3 , 2007, The EMBO journal.
[121] J. Bonventre,et al. A highly conserved tyrosine of Tim-3 is phosphorylated upon stimulation by its ligand galectin-9. , 2006, Biochemical and biophysical research communications.
[122] F. Triebel,et al. A soluble LAG-3 protein as an immunopotentiator for therapeutic vaccines: Preclinical evaluation of IMP321. , 2006, Vaccine.
[123] V. Kuchroo,et al. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity , 2005, Nature Immunology.
[124] D. Voelker. Protein and lipid motifs regulate phosphatidylserine traffic in yeast. , 2005, Biochemical Society transactions.
[125] A. Shibuya,et al. Requirement of the serine at residue 329 for lipid raft recruitment of DNAM-1 (CD226). , 2005, International immunology.
[126] S. Wildt,et al. The humanization of N-glycosylation pathways in yeast , 2005, Nature Reviews Microbiology.
[127] D. Vignali,et al. Biochemical Analysis of the Regulatory T Cell Protein Lymphocyte Activation Gene-3 (LAG-3; CD223)1 , 2004, The Journal of Immunology.
[128] A. Nomoto,et al. Ligand stimulation of CD155alpha inhibits cell adhesion and enhances cell migration in fibroblasts. , 2004, Biochemical and biophysical research communications.
[129] H. Nakauchi,et al. CD226 (DNAM-1) Is Involved in Lymphocyte Function–associated Antigen 1 Costimulatory Signal for Naive T Cell Differentiation and Proliferation , 2003, The Journal of experimental medicine.
[130] H. Rammensee,et al. Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia. , 2003, Blood.
[131] D. Vignali,et al. The CD4‐related molecule, LAG‐3 (CD223), regulates the expansion of activated T cells , 2003, European journal of immunology.
[132] D. Voelker,et al. Phosphatidylserine Transport to the Mitochondria Is Regulated by Ubiquitination* , 2002, The Journal of Biological Chemistry.
[133] D. Vignali,et al. Cutting Edge: Molecular Analysis of the Negative Regulatory Function of Lymphocyte Activation Gene-31 , 2002, The Journal of Immunology.
[134] T. Spies,et al. Broad tumor-associated expression and recognition by tumor-derived γδ T cells of MICA and MICB , 1999 .
[135] L. Caskey,et al. Cleavage of the C-terminus of NEDD8 by UCH-L3. , 1998, Biochemical and biophysical research communications.
[136] L. Lanier,et al. Protein kinase C is involved in the regulation of both signaling and adhesion mediated by DNAX accessory molecule-1 receptor. , 1998, Journal of immunology.
[137] E. Yeh,et al. Characterization of NEDD8, a Developmentally Down-regulated Ubiquitin-like Protein* , 1997, The Journal of Biological Chemistry.
[138] S. Roman-Roman,et al. LAG-3, a novel lymphocyte activation gene closely related to CD4 , 1990, The Journal of experimental medicine.
[139] Yiting Wang,et al. Phosphorylation: A Fast Switch For Checkpoint Signaling. , 2020, Advances in experimental medicine and biology.
[140] Haojie Lu,et al. Palmitoylation as a Signal for Delivery. , 2020, Advances in experimental medicine and biology.
[141] H. Clark,et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells , 2009, Nature Immunology.