130:
122:
293:: This molecule, also called CD134, has OX40L, or CD252, as its ligand. Like CD27, OX40 promotes the expansion of effector and memory T cells, however it is also noted for its ability to suppress the differentiation and activity of T-regulatory cells, and also for its regulation of cytokine production. OX40's value as a drug target primarily lies in the fact that, being transiently expressed after T-cell receptor engagement, it is only upregulated on the most recently antigen-activated T cells within inflammatory lesions. Anti-OX40 monoclonal antibodies have been shown to have clinical utility in advanced cancer. The pharma company
1971:
323:
338:: The Adenosine A2A receptor is regarded as an important checkpoint in cancer therapy because adenosine in the immune microenvironment, leading to the activation of the A2a receptor, is negative immune feedback loop and the tumor microenvironment has relatively high concentrations of adenosine. Recently, the role of the A2B receptor in the immune system has been demonstrated. Studies propose that in tissues where they are co-expressed, A2A and A2B form dimers under the majority control of the A2B receptor.
25:
1267:
356:: This molecule, short for B and T Lymphocyte Attenuator and also called CD272, has HVEM (Herpesvirus Entry Mediator) as its ligand. Surface expression of BTLA is gradually downregulated during differentiation of human CD8+ T cells from the naive to effector cell phenotype, however tumor-specific human CD8+ T cells express high levels of BTLA.
313:: This molecule, short for Inducible T-cell costimulator, and also called CD278, is expressed on activated T cells. Its ligand is ICOSL, expressed mainly on B cells and dendritic cells. The molecule seems to be important in T cell effector function. The American biotechnology company Jounce Therapeutics is developing an ICOS agonist.
376:: short for Indoleamine 2,3-dioxygenase, is a tryptophan catabolic enzyme with immune-inhibitory properties. Another important molecule is TDO, tryptophan 2,3-dioxygenase. IDO is known to suppress T and NK cells, generate and activate Tregs and myeloid-derived suppressor cells, and promote tumour angiogenesis.
279:: When this molecule, also called 4-1BB, is bound by CD137 ligand, the result is T-cell proliferation. CD137-mediated signaling is also known to protect T cells, and in particular, CD8+ T cells from activation-induced cell death. The German biotech company Pieris Pharmaceuticals has developed an engineered
1593:
Prieto-Díaz, Rubén; González-Gómez, Manuel; Fojo-Carballo, Hugo; Azuaje, Jhonny; El
Maatougui, Abdelaziz; Majellaro, Maria; Loza, María I.; Brea, José; Fernández-Dueñas, Víctor; Paleo, M. Rita; Díaz-Holguín, Alejandro; Garcia-Pinel, Beatriz; Mallo-Abreu, Ana; Estévez, Juan C.; Andújar-Arias, Antonio
250:
and transiently expressed on the surface of activated CD4+ T cells, as its ligand. CD40 signaling is known to ‘license’ dendritic cells to mature and thereby trigger T-cell activation and differentiation. A now-defunct
Seattle-based biotechnology company called VLST in-licensed an anti-CD40 agonist
344:: also called CD276, was originally understood to be a co-stimulatory molecule but is now regarded as co-inhibitory. The American biotechnology company MacroGenics is working on MGA271 is an Fc-optimized monoclonal antibody that targets B7-H3. B7-H3’s receptors have not yet been identified.
466:: short for T-cell Immunoglobulin domain and Mucin domain 3, expresses on activated human CD4+ T cells and regulates Th1 and Th17 cytokines. TIM-3 acts as a negative regulator of Th1/Tc1 function by triggering cell death upon interaction with its ligand,
476:: Short for V-domain Ig suppressor of T cell activation, VISTA is primarily expressed on hematopoietic cells so that consistent expression of VISTA on leukocytes within tumors may allow VISTA blockade to be effective across a broad range of solid tumors.
206:: This molecule supports antigen-specific expansion of naïve T cells and is vital for the generation of T cell memory. CD27 is also a memory marker of B cells. CD27's activity is governed by the transient availability of its ligand,
396:: short for Lymphocyte Activation Gene-3, works to suppress an immune response by action to Tregs as well as direct effects on CD8+ T cells. Bristol-Myers Squibb is in Phase I with an anti-LAG3 monoclonal antibody called BMS-986016.
507:; this idea is often referred to as immune checkpoint blockade, or simply checkpoint blockade. Checkpoint inhibitor drugs have seen growth in pharmaceutical research in cancer by companies including Bristol-Myers Squibb,
1094:
1984:
Kolar P, Knieke K, Hegel JK, Quandt D, Burmester GR, Hoff H, Brunner-Weinzierl MC (January 2009). "CTLA-4 (CD152) controls homeostasis and suppressive capacity of regulatory T cells in mice".
486:(Sialic acid-binding immunoglobulin-type lectin 9, also designated as CD329) are proteins found on the surface of various immune cells, including natural killer cells and macrophages (
307:. Antibodies to GITR have been shown to promote an anti-tumor response through loss of Treg lineage stability. The biotech company TG Therapeutics is working on anti-GITR antibodies
1033:
631:
Hendriks J, Gravestein LA, Tesselaar K, van Lier RA, Schumacher TN, Borst J (November 2000). "CD27 is required for generation and long-term maintenance of T cell immunity".
148:, which prevents the immune system from attacking cells indiscriminately. However, some cancers can protect themselves from attack by stimulating immune checkpoint targets.
2704:
1716:
Chapoval AI, Ni J, Lau JS, Wilcox RA, Flies DB, Liu D, et al. (March 2001). "B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production".
1098:
303:: short for Glucocorticoid-Induced TNFR family Related gene, prompts T cell expansion, including Treg expansion. The ligand for GITR is mainly expressed on
1421:"TG Therapeutics Enters Into a Global Collaboration With Checkpoint Therapeutics to Develop and Commercialize Novel Immuno-Oncology Targeted Antibodies"
46:
39:
224:: This molecule is constitutively expressed on almost all human CD4+ T cells and on around half of all CD8 T cells. Binding with its two ligands are
1005:"Nektar and MD Anderson Cancer Center Announce Phase 1/2 Clinical Research Collaboration for NKTR-214, a CD122-Biased Immuno-Stimulatory Cytokine"
607:
297:
has three drugs in development targeting OX40: MEDI0562 is a humanised OX40 agonist; MEDI6469, murine OX4 agonist; and MEDI6383, an OX40 agonist
494:). SIGLECs 7 and 9 suppress the immune function of these cells by binding to terminal sialic acid on glycans that cover the surface of cells.
1095:"Pieris Pharmaceuticals to present data on novel anti-CD137 and HER2 bispecific immuno-oncology program at UBS Global Healthcare Conference"
936:
460:, which gained FDA approval in 2017. An advantage of targeting PD-1 is that it can restore immune function in the tumor microenvironment.
199:—CD27, CD40, OX40, GITR and CD137. Another two stimulatory checkpoint molecules belong to the B7-CD28 superfamily—CD28 itself and ICOS.
1004:
585:
379:
746:"The CD27 and CD70 costimulatory pathway inhibits effector function of T helper 17 cells and attenuates associated autoimmunity"
129:
89:
853:"Monoclonal antibody TGN1412 trial failure explained by species differences in CD28 expression on CD4+ effector memory T-cells"
61:
2386:
184:
785:
214:
effector cell function. The
American biotech company Celldex Therapeutics is working on CDX-1127, an agonistic anti-CD27
68:
961:
Boyman O, Sprent J (February 2012). "The role of interleukin-2 during homeostasis and activation of the immune system".
812:"Agonist anti-human CD27 monoclonal antibody induces T cell activation and tumor immunity in human CD27-transgenic mice"
370:, which gained FDA approval in March 2011. Expression of CTLA-4 on Treg cells serves to control T cell proliferation.
108:
350:: also called VTCN1, is expressed by tumor cells and tumor-associated macrophages and plays a role in tumour escape.
2034:
Syn NL, Teng MW, Mok TS, Soo RA (December 2017). "De-novo and acquired resistance to immune checkpoint targeting".
456:, which gained FDA approval in September 2014. The checkpoint is also the target of EMD Serono (Merck KGaA)'s drug
75:
1881:"Novel recombinant human b7-h4 antibodies overcome tumoral immune escape to potentiate T-cell antitumor responses"
1373:"GITR pathway activation abrogates tumor immune suppression through loss of regulatory T cell lineage stability"
1538:
adenosine receptor antagonists rescue lymphocyte activity in adenosine-producing patient-derived cancer models"
269:
beta sub-unit, is known to increase proliferation of CD8+ effector T cells. The
American biotechnology company
1596:"Exploring the Effect of Halogenation in a Series of Potent and Selective A 2B Adenosine Receptor Antagonists"
57:
1930:"BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination"
2161:"LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems"
414:. Genetic and pharmacological inhibition of NOX2 in myeloid cells improves anti-tumor functions of adjacent
236:'superagonist' which caused severe inflammatory reactions in the first-in-man study in London in March 2006.
1832:"B7-H1 and B7-H3 are independent predictors of poor prognosis in patients with non-small cell lung cancer"
1218:
Curti BD, Kovacsovics-Bankowski M, Morris N, Walker E, Chisholm L, Floyd K, et al. (December 2013).
373:
273:
is working on NKTR-214, a CD122-biased immune-stimulatory cytokine Phase I results announced in Nov 2016.
2508:
Stanczak MA, Siddiqui SS, Trefny MP, Thommen DS, Boligan KF, von Gunten S, et al. (November 2018).
2365:
Zhu C, Anderson AC, Kuchroo VK (August 11, 2010). "TIM-3 and its regulatory role in immune responses".
1291:"GITR, a member of the TNF receptor superfamily, is costimulatory to mouse T lymphocyte subpopulations"
503:
Drugs or drug candidates that inhibit/block the inhibitory checkpoint molecules are sometimes known as
1761:"B7-H3 is a potent inhibitor of human T-cell activation: No evidence for B7-H3 and TREML2 interaction"
2316:
Hastings WD, Anderson DE, Kassam N, Koguchi K, Greenfield EA, Kent SC, et al. (September 2009).
2069:
Prendergast GC, Smith C, Thomas S, Mandik-Nayak L, Laury-Kleintop L, Metz R, Muller AJ (July 2014).
1970:
218:
which in animal models has been shown to be effective in the context of T cell receptor stimulation.
121:
304:
243:
196:
2159:
Grosso JF, Kelleher CC, Harris TJ, Maris CH, Hipkiss EL, De Marzo A, et al. (November 2007).
1659:
Hinz S, Navarro G, Borroto-Escuela D, Seibt BF, Ammon YC, de
Filippo E, et al. (March 2018).
1420:
1289:
Ronchetti S, Zollo O, Bruscoli S, Agostini M, Bianchini R, Nocentini G, et al. (March 2004).
2510:"Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells"
744:
Coquet JM, Middendorp S, van der Horst G, Kind J, Veraar EA, Xiao Y, et al. (January 2013).
411:
35:
2213:
for "Safety Study of Anti-LAG-3 With and
Without Anti-PD-1 in the Treatment of Solid Tumors" at
362:: short for Cytotoxic T-Lymphocyte-Associated protein 4 and also called CD152, is the target of
2735:
1808:
431:
335:
331:
82:
2071:"Indoleamine 2,3-dioxygenase pathways of pathogenic inflammation and immune escape in cancer"
1879:
Dangaj D, Lanitis E, Zhao A, Joshi S, Cheng Y, Sandaltzopoulos R, et al. (August 2013).
1809:"MacroGenics Provides Update on Corporate Progress and First Quarter 2015 Financial Results"
1442:
Burmeister Y, Lischke T, Dahler AC, Mages HW, Lam KP, Coyle AJ, et al. (January 2008).
504:
363:
156:
152:
1012:
810:
He LZ, Prostak N, Thomas LJ, Vitale L, Weidlick J, Crocker A, et al. (October 2013).
709:
Borst J, Hendriks J, Xiao Y (June 2005). "CD27 and CD70 in T cell and B cell activation".
8:
2318:"TIM-3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines"
1928:
Derré L, Rivals JP, Jandus C, Pastor S, Rimoldi D, Romero P, et al. (January 2010).
387:
270:
215:
1759:
Leitner J, Klauser C, Pickl WF, Stöckl J, Majdic O, Bardet AF, et al. (July 2009).
1071:
1046:
581:
2681:
2656:
2632:
2607:
2588:
2534:
2509:
2485:
2460:
2459:
Lines JL, Pantazi E, Mak J, Sempere LF, Wang L, O'Connell S, et al. (April 2014).
2436:
2412:"VISTA, a novel mouse Ig superfamily ligand that negatively regulates T cell responses"
2411:
2342:
2317:
2252:
2227:
2214:
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2160:
2095:
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1905:
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1509:
1484:
1397:
1372:
1371:
Schaer DA, Budhu S, Liu C, Bryson C, Malandro N, Cohen A, et al. (November 2013).
1244:
1219:
1195:
1170:
1146:
1121:
986:
877:
852:
851:
Eastwood D, Findlay L, Poole S, Bird C, Wadhwa M, Moore M, et al. (October 2010).
656:
558:
533:
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913:
2686:
2637:
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2539:
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2441:
2410:
Wang L, Rubinstein R, Lines JL, Wasiuk A, Ahonen C, Guo Y, et al. (March 2011).
2392:
2382:
2347:
2298:
2257:
2190:
2141:
2118:
Huang CT, Workman CJ, Flies D, Pan X, Marson AL, Zhou G, et al. (October 2004).
2100:
2051:
2001:
1959:
1910:
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256:
232:, expressed on dendritic cells, prompts T cell expansion. CD28 was the target of the
2592:
1745:
1532:
Tay AH, Prieto-Díaz R, Neo S, Tong L, Chen X, Carannante V, et al. (May 2022).
1169:
Weinberg AD, Morris NP, Kovacsovics-Bankowski M, Urba WJ, Curti BD (November 2011).
990:
660:
322:
2676:
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2627:
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2529:
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172:
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2209:
1896:
1388:
1235:
2136:
2119:
1611:
762:
745:
482:(Sialic acid-binding immunoglobulin-type lectin 7, also designated as CD328) and
473:
1485:"A2aR antagonists: Next generation checkpoint blockade for cancer immunotherapy"
155:
due to their potential for use in multiple types of cancers. Currently approved
1500:
1460:
1443:
1062:
789:
508:
145:
2086:
1684:
1034:
Immunotherapy, NKTR-214, Shows
Activity Against Solid Tumors in Clinical Trial
900:
O'Sullivan B, Thomas R (January 1, 2003). "CD40 and dendritic cell function".
722:
210:, on lymphocytes and dendritic cells. CD27 costimulation is known to suppress
2729:
1847:
1619:
1553:
828:
811:
453:
407:
390:. Bristol-Myers Squibb is working on Lirilumab, a monoclonal antibody to KIR.
266:
141:
133:
Immune checkpoints of immunosuppressive actions associated with breast cancer
2293:
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2005:
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730:
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652:
567:
423:
176:
2333:
1776:
1348:
1331:
1307:
1290:
1220:"OX40 is a potent immune-stimulating target in late-stage cancer patients"
2427:
1122:"The significance of OX40 and OX40L to T-cell biology and immune disease"
512:
383:
294:
382:: short for Killer-cell Immunoglobulin-like Receptor, is a receptor for
2378:
1830:
Mao Y, Li W, Chen K, Xie Y, Liu Q, Yao M, et al. (February 2015).
1444:"ICOS controls the pool size of effector-memory and regulatory T cells"
1168:
687:
490:) and neutrophils, macrophages, dendritic cells and activated T-cells (
367:
326:
Cancer
Therapy by Inhibition of Negative Immune Regulation (CTLA4, PD1)
180:
2525:
2243:
1997:
1217:
2176:
1945:
280:
242:: This molecule, found on a variety of immune system cells including
2672:
2623:
2575:
2558:
974:
549:
24:
1329:
630:
457:
452:. This checkpoint is the target of Merck & Co.'s melanoma drug
415:
2068:
1729:
644:
743:
491:
487:
483:
479:
444:: short for Programmed Death 1 (PD-1) receptor, has two ligands,
427:
419:
233:
1332:"GITR/GITRL: more than an effector T cell co-stimulatory system"
2608:"Siglec-mediated regulation of immune cell function in disease"
1658:
608:"James P Allison and Tasuku Honjo win Nobel prize for medicine"
467:
463:
359:
252:
1330:
Nocentini G, Ronchetti S, Cuzzocrea S, Riccardi C (May 2007).
1288:
2507:
2315:
449:
445:
403:
347:
341:
310:
276:
262:
247:
168:
160:
2657:"The blockade of immune checkpoints in cancer immunotherapy"
1441:
534:"The blockade of immune checkpoints in cancer immunotherapy"
441:
399:
393:
353:
300:
290:
284:
239:
229:
225:
221:
211:
207:
203:
164:
2461:"VISTA is an immune checkpoint molecule for human T cells"
937:"Cancer 'Miracle' Patients Studied Anew for Disease Clues"
426:
in humans and experimental animals. NOX2 is the target of
2409:
2277:"Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies"
2158:
1758:
1665:
receptor ligand recognition and signaling is blocked by A
195:
Four stimulatory checkpoint molecules are members of the
850:
402:: short for nicotinamide adenine dinucleotide phosphate
1927:
435:
2605:
2458:
2225:
1983:
1878:
259:
acquired this project when VLST was shut down in 2013.
1531:
1097:. Pieris Pharmaceuticals. 19 May 2015. Archived from
1045:
Singh R, Kim YH, Lee SJ, Eom HS, Choi BK (Feb 2024).
809:
2606:
Macauley MS, Crocker PR, Paulson JC (October 2014).
2117:
1370:
1171:"Science gone translational: the OX40 agonist story"
899:
674:
Agematsu K (April 2000). "Memory B cells and CD27".
2556:
2228:"NOX2 in autoimmunity, tumor growth and metastasis"
1715:
190:
2364:
2226:Martner A, Aydin E, Hellstrand K (February 2019).
1489:Computational and Structural Biotechnology Journal
1119:
317:
708:
125:Immune checkpoints in the tumour microenvironment
2727:
197:tumor necrosis factor (TNF) receptor superfamily
151:Inhibitory checkpoint molecules are targets for
786:"CDX-1127 – Monoclonal Antibody Targeting CD27"
498:
2559:"Siglecs and their roles in the immune system"
2557:Crocker PR, Paulson JC, Varki A (April 2007).
1044:
582:"2014 Tang Prize in Biopharmaceutical Science"
2367:Current Topics in Microbiology and Immunology
2274:
2033:
1482:
1120:Croft M, So T, Duan W, Soroosh P (May 2009).
171:. For the related basic science discoveries,
2705:"Cancer drugs are getting better and dearer"
1829:
1483:Leone RD, Lo YC, Powell JD (April 8, 2015).
1051:Experimental & Molecular Medicine volume
960:
1047:"4-1BB immunotherapy: advances and hurdles"
525:
599:
255:in 2012. The Swiss pharmaceutical company
2680:
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2533:
2484:
2435:
2341:
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2135:
2094:
1953:
1904:
1855:
1784:
1692:
1627:
1561:
1508:
1459:
1396:
1347:
1306:
1243:
1194:
1145:
1070:
876:
827:
761:
557:
109:Learn how and when to remove this message
673:
321:
128:
120:
2654:
531:
181:Tang Prize in Biopharmaceutical Science
2728:
788:. Celldex Therapeutics. Archived from
605:
45:Please improve this article by adding
2514:The Journal of Clinical Investigation
2275:Philips GK, Atkins M (January 2015).
2165:The Journal of Clinical Investigation
2120:"Role of LAG-3 in regulatory T cells"
2029:
2027:
2025:
2023:
2021:
2019:
2017:
2015:
1934:The Journal of Clinical Investigation
185:Nobel Prize in Physiology or Medicine
2416:The Journal of Experimental Medicine
934:
430:that has gained approval for use in
18:
1542:Journal for Immunotherapy of Cancer
406:oxidase isoform 2, is an enzyme of
13:
2012:
283:that is bi-specific for CD137 and
14:
2747:
914:10.1615/critrevimmunol.v23.i12.50
410:that generates immunosuppressive
144:. These pathways are crucial for
2075:Cancer Immunology, Immunotherapy
1969:
1187:10.1111/j.1600-065x.2011.01069.x
1138:10.1111/j.1600-065x.2009.00766.x
869:10.1111/j.1476-5381.2010.00922.x
191:Stimulatory checkpoint molecules
23:
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2648:
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1977:
1921:
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1823:
1801:
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1709:
1652:
1586:
1525:
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1435:
1423:. TG Therapeutics. 4 March 2015
1413:
1364:
1323:
1282:
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1211:
1162:
1113:
1087:
1038:
1027:
997:
954:
928:
893:
857:British Journal of Pharmacology
844:
588:from the original on 2017-10-20
318:Inhibitory checkpoint molecules
16:Regulators of the immune system
2322:European Journal of Immunology
1765:European Journal of Immunology
1600:Journal of Medicinal Chemistry
1336:European Journal of Immunology
1295:European Journal of Immunology
1011:. June 2, 2015. Archived from
902:Critical Reviews in Immunology
803:
778:
737:
702:
667:
624:
574:
265:: This molecule, which is the
246:has CD40L, otherwise known as
1:
2477:10.1158/0008-5472.CAN-13-1504
2048:10.1016/s1470-2045(17)30607-1
1897:10.1158/0008-5472.can-12-3457
1389:10.1158/2326-6066.cir-13-0086
1236:10.1158/0008-5472.can-12-4174
711:Current Opinion in Immunology
518:
47:secondary or tertiary sources
2137:10.1016/j.immuni.2004.08.010
1612:10.1021/acs.jmedchem.2c01768
1270:. AstraZeneca. 24 April 2015
763:10.1016/j.immuni.2012.09.009
676:Histology and Histopathology
499:Immune checkpoint inhibitors
7:
10:
2752:
2612:Nature Reviews. Immunology
2563:Nature Reviews. Immunology
1501:10.1016/j.csbj.2015.03.008
1461:10.4049/jimmunol.180.2.774
1377:Cancer Immunology Research
1063:10.1038/s12276-023-01136-4
963:Nature Reviews. Immunology
2655:Pardoll DM (March 2012).
2087:10.1007/s00262-014-1549-4
1811:. MacroGenics. 6 May 2015
1685:10.18632/oncotarget.24423
935:Zimm A (April 12, 2014).
723:10.1016/j.coi.2005.04.004
532:Pardoll DM (March 2012).
251:monoclonal antibody from
2281:International Immunology
2232:The Journal of Pathology
1986:Arthritis and Rheumatism
1848:10.18632/oncotarget.3097
1554:10.1136/jitc-2022-004592
829:10.4049/jimmunol.1300409
511:, Merck KGaA, Roche and
305:antigen presenting cells
244:antigen presenting cells
606:Devlin H (2018-10-01).
412:reactive oxygen species
2661:Nature Reviews. Cancer
2207:Clinical trial number
538:Nature Reviews. Cancer
432:acute myeloid leukemia
327:
267:Interleukin-2 receptor
140:are regulators of the
134:
126:
34:relies excessively on
2334:10.1002/eji.200939274
2294:10.1093/intimm/dxu095
1777:10.1002/eji.200839028
1448:Journal of Immunology
1349:10.1002/eji.200636933
1308:10.1002/eji.200324804
1175:Immunological Reviews
1126:Immunological Reviews
816:Journal of Immunology
505:checkpoint inhibitors
325:
157:checkpoint inhibitors
132:
124:
2428:10.1084/jem.20100619
2036:The Lancet. Oncology
388:Natural Killer cells
364:Bristol-Myers Squibb
153:cancer immunotherapy
1679:(17): 13593–13611.
1015:on 19 December 2017
1009:Nektar Therapeutics
271:Nektar Therapeutics
216:monoclonal antibody
58:"Immune checkpoint"
2379:10.1007/82_2010_84
2215:ClinicalTrials.gov
688:10.14670/HH-15.573
422:and also triggers
328:
138:Immune checkpoints
135:
127:
2526:10.1172/JCI120612
2520:(11): 4912–4923.
2388:978-3-642-19544-0
2244:10.1002/path.5175
2171:(11): 3383–3392.
2042:(12): e731–e741.
1998:10.1002/art.24181
1891:(15): 4820–4829.
1718:Nature Immunology
1230:(24): 7189–7198.
1101:on 3 October 2018
633:Nature Immunology
366:'s melanoma drug
119:
118:
111:
93:
2743:
2720:
2719:
2717:
2716:
2701:
2695:
2694:
2684:
2652:
2646:
2645:
2635:
2603:
2597:
2596:
2578:
2554:
2548:
2547:
2537:
2505:
2499:
2498:
2488:
2471:(7): 1924–1932.
2456:
2450:
2449:
2439:
2407:
2401:
2400:
2362:
2356:
2355:
2345:
2328:(9): 2492–2501.
2313:
2307:
2306:
2296:
2272:
2266:
2265:
2255:
2223:
2217:
2205:
2199:
2198:
2188:
2177:10.1172/jci31184
2156:
2150:
2149:
2139:
2115:
2109:
2108:
2098:
2066:
2060:
2059:
2031:
2010:
2009:
1981:
1975:
1974:
1973:
1967:
1957:
1946:10.1172/jci40070
1925:
1919:
1918:
1908:
1876:
1870:
1869:
1859:
1842:(5): 3452–3461.
1827:
1821:
1820:
1818:
1816:
1805:
1799:
1798:
1788:
1771:(7): 1754–1764.
1756:
1750:
1749:
1713:
1707:
1706:
1696:
1656:
1650:
1649:
1631:
1590:
1584:
1583:
1565:
1529:
1523:
1522:
1512:
1480:
1474:
1473:
1463:
1439:
1433:
1432:
1430:
1428:
1417:
1411:
1410:
1400:
1368:
1362:
1361:
1351:
1342:(5): 1165–1169.
1327:
1321:
1320:
1310:
1286:
1280:
1279:
1277:
1275:
1268:"Q1 2015 Result"
1264:
1258:
1257:
1247:
1215:
1209:
1208:
1198:
1166:
1160:
1159:
1149:
1117:
1111:
1110:
1108:
1106:
1091:
1085:
1084:
1074:
1042:
1036:
1031:
1025:
1024:
1022:
1020:
1001:
995:
994:
958:
952:
951:
949:
947:
932:
926:
925:
897:
891:
890:
880:
848:
842:
841:
831:
822:(8): 4174–4183.
807:
801:
800:
798:
797:
782:
776:
775:
765:
741:
735:
734:
706:
700:
699:
671:
665:
664:
628:
622:
621:
619:
618:
603:
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571:
561:
529:
173:James P. Allison
114:
107:
103:
100:
94:
92:
51:
27:
19:
2751:
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2744:
2742:
2741:
2740:
2726:
2725:
2724:
2723:
2714:
2712:
2703:
2702:
2698:
2673:10.1038/nrc3239
2653:
2649:
2624:10.1038/nri3737
2618:(10): 653–666.
2604:
2600:
2576:10.1038/nri2056
2555:
2551:
2506:
2502:
2465:Cancer Research
2457:
2453:
2408:
2404:
2389:
2363:
2359:
2314:
2310:
2273:
2269:
2224:
2220:
2206:
2202:
2157:
2153:
2116:
2112:
2067:
2063:
2032:
2013:
1982:
1978:
1968:
1926:
1922:
1885:Cancer Research
1877:
1873:
1828:
1824:
1814:
1812:
1807:
1806:
1802:
1757:
1753:
1714:
1710:
1668:
1664:
1657:
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1591:
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1526:
1481:
1477:
1440:
1436:
1426:
1424:
1419:
1418:
1414:
1369:
1365:
1328:
1324:
1287:
1283:
1273:
1271:
1266:
1265:
1261:
1224:Cancer Research
1216:
1212:
1167:
1163:
1118:
1114:
1104:
1102:
1093:
1092:
1088:
1043:
1039:
1032:
1028:
1018:
1016:
1003:
1002:
998:
975:10.1038/nri3156
959:
955:
945:
943:
933:
929:
908:(1–2): 83–107.
898:
894:
849:
845:
808:
804:
795:
793:
784:
783:
779:
742:
738:
707:
703:
672:
668:
629:
625:
616:
614:
604:
600:
591:
589:
580:
579:
575:
550:10.1038/nrc3239
530:
526:
521:
501:
320:
193:
115:
104:
98:
95:
52:
50:
44:
40:primary sources
28:
17:
12:
11:
5:
2749:
2739:
2738:
2722:
2721:
2696:
2667:(4): 252–264.
2647:
2598:
2569:(4): 255–266.
2549:
2500:
2451:
2422:(3): 577–592.
2402:
2387:
2357:
2308:
2267:
2238:(2): 151–154.
2218:
2200:
2151:
2130:(4): 503–513.
2110:
2081:(7): 721–735.
2061:
2011:
1992:(1): 123–132.
1976:
1940:(1): 157–167.
1920:
1871:
1822:
1800:
1751:
1724:(3): 269–274.
1708:
1666:
1662:
1651:
1606:(1): 890–912.
1594:(2022-12-14).
1585:
1548:(5): e004592.
1535:
1524:
1475:
1454:(2): 774–782.
1434:
1412:
1383:(5): 320–331.
1363:
1322:
1301:(3): 613–622.
1281:
1259:
1210:
1181:(1): 218–231.
1161:
1132:(1): 173–191.
1112:
1086:
1037:
1026:
996:
969:(3): 180–190.
953:
927:
892:
863:(3): 512–526.
843:
802:
777:
736:
717:(3): 275–281.
701:
682:(2): 573–576.
666:
639:(5): 433–440.
623:
598:
573:
544:(4): 252–264.
523:
522:
520:
517:
500:
497:
496:
495:
477:
471:
461:
439:
397:
391:
377:
371:
357:
351:
345:
339:
319:
316:
315:
314:
308:
298:
288:
274:
260:
237:
219:
192:
189:
146:self-tolerance
117:
116:
31:
29:
22:
15:
9:
6:
4:
3:
2:
2748:
2737:
2736:Immune system
2734:
2733:
2731:
2710:
2709:The Economist
2706:
2700:
2692:
2688:
2683:
2678:
2674:
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2504:
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2300:
2295:
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2259:
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2222:
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2212:
2211:
2204:
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2187:
2182:
2178:
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2166:
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2155:
2147:
2143:
2138:
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2097:
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2057:
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2049:
2045:
2041:
2037:
2030:
2028:
2026:
2024:
2022:
2020:
2018:
2016:
2007:
2003:
1999:
1995:
1991:
1987:
1980:
1972:
1965:
1961:
1956:
1951:
1947:
1943:
1939:
1935:
1931:
1924:
1916:
1912:
1907:
1902:
1898:
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1810:
1804:
1796:
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1787:
1782:
1778:
1774:
1770:
1766:
1762:
1755:
1747:
1743:
1739:
1735:
1731:
1730:10.1038/85339
1727:
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1355:
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1263:
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1251:
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1237:
1233:
1229:
1225:
1221:
1214:
1206:
1202:
1197:
1192:
1188:
1184:
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1176:
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1135:
1131:
1127:
1123:
1116:
1100:
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1082:
1078:
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1052:
1048:
1041:
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992:
988:
984:
980:
976:
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942:
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923:
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870:
866:
862:
858:
854:
847:
839:
835:
830:
825:
821:
817:
813:
806:
792:on 2018-10-03
791:
787:
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773:
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724:
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689:
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681:
677:
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658:
654:
650:
646:
645:10.1038/80877
642:
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583:
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569:
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459:
455:
451:
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433:
429:
425:
421:
417:
413:
409:
408:myeloid cells
405:
401:
398:
395:
392:
389:
386:molecules on
385:
381:
378:
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372:
369:
365:
361:
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149:
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143:
142:immune system
139:
131:
123:
113:
110:
102:
99:November 2018
91:
88:
84:
81:
77:
74:
70:
67:
63:
60: –
59:
55:
54:Find sources:
48:
42:
41:
37:
32:This article
30:
26:
21:
20:
2713:. Retrieved
2711:. 2017-05-04
2708:
2699:
2664:
2660:
2650:
2615:
2611:
2601:
2566:
2562:
2552:
2517:
2513:
2503:
2468:
2464:
2454:
2419:
2415:
2405:
2370:
2366:
2360:
2325:
2321:
2311:
2287:(1): 39–46.
2284:
2280:
2270:
2235:
2231:
2221:
2208:
2203:
2168:
2164:
2154:
2127:
2123:
2113:
2078:
2074:
2064:
2039:
2035:
1989:
1985:
1979:
1937:
1933:
1923:
1888:
1884:
1874:
1839:
1835:
1825:
1813:. Retrieved
1803:
1768:
1764:
1754:
1721:
1717:
1711:
1676:
1672:
1661:"Adenosine A
1654:
1603:
1599:
1588:
1545:
1541:
1527:
1492:
1488:
1478:
1451:
1447:
1437:
1425:. Retrieved
1415:
1380:
1376:
1366:
1339:
1335:
1325:
1298:
1294:
1284:
1272:. Retrieved
1262:
1227:
1223:
1213:
1178:
1174:
1164:
1129:
1125:
1115:
1103:. Retrieved
1099:the original
1089:
1057:(1): 32–39.
1054:
1050:
1040:
1029:
1017:. Retrieved
1013:the original
1008:
999:
966:
962:
956:
944:. Retrieved
940:
930:
905:
901:
895:
860:
856:
846:
819:
815:
805:
794:. Retrieved
790:the original
780:
756:(1): 53–65.
753:
749:
739:
714:
710:
704:
679:
675:
669:
636:
632:
626:
615:. Retrieved
612:the Guardian
611:
601:
590:. Retrieved
576:
541:
537:
527:
502:
424:autoimmunity
194:
177:Tasuku Honjo
150:
137:
136:
105:
96:
86:
79:
72:
65:
53:
33:
2210:NCT01968109
1495:: 265–272.
513:AstraZeneca
434:within the
384:MHC Class I
295:AstraZeneca
2715:2017-05-19
1836:Oncotarget
1673:Oncotarget
1669:receptors"
796:2015-06-04
617:2018-10-01
592:2016-06-18
519:References
468:galectin-9
69:newspapers
36:references
1646:254759241
1620:0022-2623
1580:248858436
941:Bloomberg
281:lipocalin
187:in 2018.
2730:Category
2691:22437870
2642:25234143
2593:26722878
2585:17380156
2544:30130255
2495:24691993
2446:21383057
2397:20700701
2373:: 1–15.
2352:19676072
2303:25323844
2262:30270440
2195:17932562
2146:15485628
2124:Immunity
2105:24711084
2056:29208439
2006:19116935
1964:20038811
1915:23722540
1866:25609202
1795:19544488
1746:43480199
1738:11224528
1703:29568380
1638:36517209
1572:35580926
1519:25941561
1470:18178815
1407:24416730
1358:17407102
1317:14991590
1254:24177180
1205:22017441
1156:19426222
1081:38172595
1072:10834507
991:22680847
983:22343569
922:12906261
887:20880392
838:24026078
772:23159439
750:Immunity
731:15886117
696:10809378
661:36108378
653:11062504
586:Archived
568:22437870
458:Bavencio
454:Keytruda
416:NK cells
183:and the
179:won the
2682:4856023
2633:4191907
2535:6205408
2486:3979527
2437:3058578
2343:2759376
2253:6587556
2186:2000807
2096:4384696
1955:2799219
1906:3732560
1857:4413666
1786:2978551
1694:5862601
1629:9841532
1563:9115112
1510:4415113
1398:3885345
1245:3922072
1196:3622727
1147:2729757
1019:25 June
946:25 June
878:2990151
559:4856023
492:SIGLEC9
488:SIGLEC7
484:SIGLEC9
480:SIGLEC7
428:Ceplene
420:T cells
234:TGN1412
83:scholar
2689:
2679:
2640:
2630:
2591:
2583:
2542:
2532:
2493:
2483:
2444:
2434:
2395:
2385:
2350:
2340:
2301:
2260:
2250:
2193:
2183:
2144:
2103:
2093:
2054:
2004:
1962:
1952:
1913:
1903:
1864:
1854:
1815:5 June
1793:
1783:
1744:
1736:
1701:
1691:
1644:
1636:
1626:
1618:
1578:
1570:
1560:
1517:
1507:
1468:
1427:5 June
1405:
1395:
1356:
1315:
1274:5 June
1252:
1242:
1203:
1193:
1154:
1144:
1105:5 June
1079:
1069:
989:
981:
920:
885:
875:
836:
770:
729:
694:
659:
651:
566:
556:
368:Yervoy
360:CTLA-4
334:&
253:Pfizer
159:block
85:
78:
71:
64:
56:
2589:S2CID
1742:S2CID
1642:S2CID
1576:S2CID
987:S2CID
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