[논문]Cancer immunotherapy with T-cell targeting cytokines: IL-2 and IL-7

Kim, Ji-Hae; Lee, Kun-Joo; Lee, Seung-Woo

doi:10.5483/bmbrep.2021.54.1.257

[국내논문] Cancer immunotherapy with T-cell targeting cytokines: IL-2 and IL-7 원문보기

BMB reports, v.54 no.1, 2021년, pp.21 - 30

Kim, Ji-Hae (Department of Life Sciences, Pohang University of Science and Technology (POSTECH)) , Lee, Kun-Joo (Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH)) , Lee, Seung-Woo (Department of Life Sciences, Pohang University of Science and Technology (POSTECH))

Abstract ▼ AI-Helper

Clinical trials have demonstrated that an increased number of effector cells, especially tumor-specific T cells, is positively linked with patients' prognosis. Although the discovery of checkpoint inhibitors (CPIs) has led to encouraging progress in cancer immunotherapy, the lack of either T cells or targets for CPIs is a limitation for patients with poor prognosis. Since interleukin (IL)-2 and IL-7 are cytokines that target many aspects of T-cell responses, they have been used to treat cancers. In this review, we focus on the basic biology of how these cytokines regulate T-cell response and on the clinical trials using the cytokines against cancer. Further, we introduce several recent studies that aim to improve cytokines' biological activities and find the strategy for combination with other therapeutics.

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표/그림 (3)

그림 Fig. 1. Modification of IL-2 for anticancer therapy. (A) Mutations in CD122 (IL-2Rβ)-binding regions of IL-2 superkines (Super-IL-2) increase binding affinity of IL-2 for IL-2Rβ than CD25 (IL-2Rα). (B) The conjugation with antibody to tumor-associated antigens (TAAs) or collagen-binding domain delivers IL-2 to tumor sites. (C) The IL-2 complex with a neutralizing antibody clone S4B6 predominantly targets cells expressing dimeric IL-2Rβ𝛾. (D) Fc-fused IL-2 has a prolonged serum half-life. (E) Fc-fused mutant IL-2 shows an increased half-life with enhanced binding affinity for IL-2Rβ. (F) The conjugation of polyethylene glycol (PEG) shows increased IL-2 persistence with an inhibited IL-2Rα binding. Figure created with BioRender.com.
그림 Fig. 2. Overview of CD8 T cell immunity regulated by IL-2 and IL-7. The receptor for IL-7 is expressed on the naïve and memory T cells including precursors cells; common lymphoid progenitors (CLP), double-positive, and single-positive thymocytes, and recent thymic emigrants (RTE). IL-7 is mainly produced by stromal cells and gives a signal to IL-7Rα-expressing cells to regulate their survival, proliferation, and maintenance. By contrast, the IL-2 receptors are highly induced on activated T cells after antigenic stimulation and the cells themselves also become a major producer of IL-2. After rapid expansion, the effector T cells develop into different fates depending on the amount of IL-2 signaling. Cells expressing high levels of IL-2Rα receive strong IL-2 signaling and become short-lived effector cells showing increased expression of Blimp1, KLRG1, and cytolytic activity. Cells expressing low levels of IL-2Rα receive relatively weak IL-2 signaling and become memory precursor cells showing increased expression of IL-7Rα, CD62L, IL-2 production, and proliferation capacity but decreased expressions of effector-associated molecules above. The re-expression of IL-7Rα on memory T cells capable of maintaining the long-term survival of the cells.
그림 Fig. 3. Modification of IL-7 for anticancer therapy. (A) Adjuvant treatment of IL-7 and its receptor complex enhances the potency of cancer vaccines. (B) Intratumoral administration of IL-7-transduced DCs (DC-AdIL-7) induces direct IL-7 signals in the tumor site. (C-F) Engineered IL-7 complexes with enhanced bioactivity. (C) IL-7 complexed with IL-7Rα-Fc. (D) IL-7 complex with a monoclonal antibody clone M25. (E) IL-7 fused with the Fc region of the antibody. (F) IL-7 fused to a hybrid Fc (IgD/IgG4) has a prolonged serum half-life without cytotoxicity on target cells. Figure created with BioRender.com.

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가설 설정

(C) The IL-2 complex with a neutralizing antibody clone S4B6 predominantly targets cells expressing dimeric IL-2R. (D) Fc-fused IL-2 has a prolonged serum half-life. (E) Fc-fused mutant IL-2 shows an increased half-life with enhanced binding affinity for IL-2R.
In general, IL-2 acts as a ‘stimulus’ to induce activation of T-cell responses, whereas IL-7 acts as an ‘expander’ to increase the number of T cells, which have been more widely used to overcome the lymphopenia derived from chronic viral infections rather than from cancer. In this review, we summarize the biology of the cytokines and their clinical uses against cancer.

참고문헌 (99)

1 Chen DS Mellman I 2013 Oncology meets immunology: the cancer-immunity cycle Immunity 39 1 10 10.1016/j.immuni.2013.07.012 23890059

상세보기
2 Fridman WH Pages F Sautes-Fridman C Galon J 2012 The immune contexture in human tumours: impact on clinical outcome Nat Rev Cancer 12 298 306 10.1038/nrc3245 22419253

상세보기
3 Menetrier-Caux C Ray-Coquard I Blay JY Caux C 2019 Lymphopenia in cancer patients and its effects on response to immunotherapy: an opportunity for combination with cytokines? J Immunother Cancer 7 85 10.1186/s40425-019-0549-5 30922400

상세보기
4 Leonard WJ Lin JX O'Shea JJ 2019 The gammac family of cytokines: basic biology to therapeutic ramifications Immunity 50 832 850 10.1016/j.immuni.2019.03.028 30995502

상세보기
5 Morgan DA Ruscetti FW Gallo R 1976 Selective in vitro growth of T lymphocytes from normal human bone marrows Science 193 1007 1008 10.1126/science.181845 181845

상세보기
6 Boyman O Sprent J 2012 The role of interleukin-2 during homeostasis and activation of the immune system Nat Rev Immunol 12 180 190 10.1038/nri3156 22343569

상세보기
7 Wang X Rickert M Garcia KC 2005 Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gammac receptors Science 310 1159 1163 10.1126/science.1117893 16293754

상세보기
8 Zhang X Sun S Hwang I Tough DF Sprent J 1998 Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15 Immunity 8 591 599 10.1016/S1074-7613(00)80564-6 9620680

상세보기
9 Boyman O Kovar M Rubinstein MP Surh CD Sprent J 2006 Selective stimulation of T cell subsets with antibody-cytokine immune complexes Science 311 1924 1927 10.1126/science.1122927 16484453

상세보기
10 Sakaguchi S 2004 Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses Annu Rev Immunol 22 531 562 10.1146/annurev.immunol.21.120601.141122 15032588

상세보기
11 Liao W Lin JX Wang L Li P Leonard WJ 2011 Modulation of cytokine receptors by IL-2 broadly regulates differentiation into helper T cell lineages Nat Immunol 12 551 559 10.1038/ni.2030 21516110

상세보기
12 Yang XP Ghoreschi K Steward-Tharp SM 2011 Opposing regulation of the locus encoding IL-17 through direct, reciprocal actions of STAT3 and STAT5 Nat Immunol 12 247 254 10.1038/ni.1995 21278738

상세보기
13 Liao W Spolski R Li P 2014 Opposing actions of IL-2 and IL-21 on Th9 differentiation correlate with their differential regulation of BCL6 expression Proc Natl Acad Sci U S A 111 3508 3513 10.1073/pnas.1301138111 24550509

상세보기
14 Laurence A Tato CM Davidson TS 2007 Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation Immunity 26 371 381 10.1016/j.immuni.2007.02.009 17363300

상세보기
15 Ballesteros-Tato A Leon B Graf BA 2012 Interleukin-2 inhibits germinal center formation by limiting T follicular helper cell differentiation Immunity 36 847 856 10.1016/j.immuni.2012.02.012 22464171

상세보기
16 Sadlack B Lohler J Schorle H 1995 Generalized autoimmune disease in interleukin-2-deficient mice is triggered by an uncontrolled activation and proliferation of CD4+ T cells Eur J Immunol 25 3053 3059 10.1002/eji.1830251111 7489743

상세보기
17 Willerford DM Chen J Ferry JA Davidson L Ma A Alt FW 1995 Interleukin-2 receptor alpha chain regulates the size and content of the peripheral lymphoid compartment Immunity 3 521 530 10.1016/1074-7613(95)90180-9 7584142

상세보기
18 Suzuki H Kundig TM Furlonger C 1995 Deregulated T cell activation and autoimmunity in mice lacking interleukin-2 receptor beta Science 268 1472 1476 10.1126/science.7770771 7770771

상세보기
19 Almeida AR Legrand N Papiernik M Freitas AA 2002 Homeostasis of peripheral CD4+ T cells: IL-2R alpha and IL-2 shape a population of regulatory cells that controls CD4+ T cell numbers J Immunol 169 4850 4860 10.4049/jimmunol.169.9.4850 12391195

상세보기
20 Malek TR Yu A Vincek V Scibelli P Kong L 2002 CD4 regulatory T cells prevent lethal autoimmunity in IL-2 Rbeta-deficient mice. Implications for the nonredundant function of IL-2 Immunity 17 167 178 10.1016/S1074-7613(02)00367-9 12196288

상세보기
21 Fontenot JD Rasmussen JP Gavin MA Rudensky AY 2005 A function for interleukin 2 in Foxp3-expressing regulatory T cells Nat Immunol 6 1142 1151 10.1038/ni1263 16227984

상세보기
22 Kalia V Sarkar S Subramaniam S Haining WN Smith KA Ahmed R 2010 Prolonged interleukin-2Ralpha expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo Immunity 32 91 103 10.1016/j.immuni.2009.11.010 20096608

상세보기
23 Pipkin ME Sacks JA Cruz-Guilloty F Lichtenheld MG Bevan MJ Rao A 2010 Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells Immunity 32 79 90 10.1016/j.immuni.2009.11.012 20096607

상세보기
24 Lenardo M Chan KM Hornung F 1999 Mature T lymphocyte apoptosis--immune regulation in a dynamic and unpredictable antigenic environment Annu Rev Immunol 17 221 253 10.1146/annurev.immunol.17.1.221 10358758

상세보기
25 Rosenberg SA Lotze MT Muul LM 1985 Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer N Engl J Med 313 1485 1492 10.1056/NEJM198512053132327 3903508

상세보기
26 Rosenberg SA Lotze MT Aebersold PM Linehan WM Seipp CA White DE 1989 Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients Ann Surg 210 474 485 10.1097/00000658-198910000-00008 2679456

상세보기
27 Rosenberg SA Yang JC Topalian SL 1994 Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2 JAMA 271 907 913 10.1001/jama.1994.03510360033032 8120958

상세보기
28 Fyfe G Fisher RI Rosenberg SA Sznol M Parkinson DR Louie AC 1995 Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy J Clin Oncol 13 688 696 10.1200/JCO.1995.13.3.688 7884429

상세보기
29 Atkins MB Lotze MT Dutcher JP 1999 High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993 J Clin Oncol 17 2105 2116 10.1200/JCO.1999.17.7.2105 10561265

상세보기
30 Caligiuri MA Murray C Robertson MJ 1993 Selective modulation of human natural killer cells in vivo after prolonged infusion of low dose recombinant interleukin 2 J Clin Invest 91 123 132 10.1172/JCI116161 7678599

상세보기
31 Caligiuri MA Murray C Soiffer RJ 1991 Extended continuous infusion low-dose recombinant interleukin-2 in advanced cancer: prolonged immunomodulation without significant toxicity J Clin Oncol 9 2110 2119 10.1200/JCO.1991.9.12.2110 1960552

상세보기
32 Soiffer RJ Murray C Shapiro C 1996 Expansion and manipulation of natural killer cells in patients with metastatic cancer by low-dose continuous infusion and intermittent bolus administration of interleukin 2 Clin Cancer Res 2 493 499 9816195

상세보기
33 Fehniger TA Bluman EM Porter MM 2000 Potential mechanisms of human natural killer cell expansion in vivo during low-dose IL-2 therapy J Clin Invest 106 117 124 10.1172/JCI6218 10880055

상세보기
34 Wrangle JM Patterson A Johnson CB 2018 IL-2 and beyond in cancer immunotherapy J Interferon Cytokine Res 38 45 68 10.1089/jir.2017.0101 29443657

상세보기
35 Krieg C Letourneau S Pantaleo G Boyman O 2010 Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells Proc Natl Acad Sci U S A 107 11906 11911 10.1073/pnas.1002569107 20547866

상세보기
36 Sim GC Martin-Orozco N Jin L 2014 IL-2 therapy promotes suppressive ICOS+ Treg expansion in melanoma patients J Clin Invest 124 99 110 10.1172/JCI46266 24292706

상세보기
37 Levin AM Bates DL Ring AM 2012 Exploiting a natural conformational switch to engineer an interleukin-2 'superkine' Nature 484 529 533 10.1038/nature10975 22446627

상세보기
38 Ardolino M Azimi CS Iannello A 2014 Cytokine therapy reverses NK cell anergy in MHC-deficient tumors J Clin Invest 124 4781 4794 10.1172/JCI74337 25329698

상세보기
39 Mortara L Balza E Bruno A Poggi A Orecchia P Carnemolla B 2018 Anti-cancer therapies employing IL-2 cytokine tumor targeting: contribution of innate, adaptive and immunosuppressive cells in the antitumor efficacy Front Immunol 9 2905 10.3389/fimmu.2018.02905 30619269

상세보기
40 Ishihara J Ishihara A Sasaki K 2019 Targeted antibody and cytokine cancer immunotherapies through collagen affinity Sci Transl Med 11 eaau3259 10.1126/scitranslmed.aau3259 30971453

상세보기
41 Mostbock S 2009 Cytokine/Antibody complexes: an emerging class of immunostimulants Curr Pharm Des 15 809 825 10.2174/138161209787582174 19275644

상세보기
42 Kamimura D Sawa Y Sato M Agung E Hirano T Murakami M 2006 IL-2 in vivo activities and antitumor efficacy enhanced by an anti-IL-2 mAb J Immunol 177 306 314 10.4049/jimmunol.177.1.306 16785526

상세보기
43 Jin GH Hirano T Murakami M 2008 Combination treatment with IL-2 and anti-IL-2 mAbs reduces tumor metastasis via NK cell activation Int Immunol 20 783 789 10.1093/intimm/dxn036 18448458

상세보기
44 Roopenian DC Akilesh S 2007 FcRn: the neonatal Fc receptor comes of age Nat Rev Immunol 7 715 725 10.1038/nri2155 17703228

상세보기
45 Zhu EF Gai SA Opel CF 2015 Synergistic innate and adaptive immune response to combination immunotherapy with antitumor antigen antibodies and extended serum half-life IL-2 Cancer Cell 27 489 501 10.1016/j.ccell.2015.03.004 25873172

상세보기
46 Sun Z Ren Z Yang K 2019 A next-generation tumor-targeting IL-2 preferentially promotes tumor-infiltrating CD8(+) T-cell response and effective tumor control Nat Commun 10 3874 10.1038/s41467-019-11782-w 31462678

상세보기
47 Yang JC Topalian SL Schwartzentruber DJ 1995 The use of polyehylene glycol-modified interleukin-2 (PEG-IL-2) in the treatment of patients with metastatic renal cell carcinoma and melanoma Cancer 76 687 694 10.1002/1097-0142(19950815)76:4<687::AID-CNCR2820760424>3.0.CO;2-M 8625167

상세보기
48 Charych DH Hoch U Langowski JL 2016 NKTR-214, an engineered cytokine with biased IL2 receptor binding, increased tumor exposure, and marked efficacy in mouse tumor Models Clin Cancer Res 22 680 690 10.1158/1078-0432.CCR-15-1631 26832745

상세보기
49 Sharma M Khong H Fa'ak F 2020 Bempegaldesleukin selectively depletes intratumoral Tregs and potentiates T cell-mediated cancer therapy Nat Commun 11 661 10.1038/s41467-020-14471-1 32005826

상세보기
50 Mackall CL Fry TJ Gress RE 2011 Harnessing the biology of IL-7 for therapeutic application Nat Rev Immunol 11 330 342 10.1038/nri2970 21508983

상세보기
51 Link A Vogt TK Favre S 2007 Fibroblastic reticular cells in lymph nodes regulate the homeostasis of naive T cells Nat Immunol 8 1255 1265 10.1038/ni1513 17893676

상세보기
52 Kim GY Hong C Park JH 2011 Seeing is believing: illuminating the source of in vivo interleukin-7 Immune Netw 11 1 10 10.4110/in.2011.11.1.1 21494371

원문보기 상세보기
53 Guimond M Veenstra RG Grindler DJ 2009 Inter-leukin 7 signaling in dendritic cells regulates the homeostatic proliferation and niche size of CD4 + T cells Nat Immunol 10 149 157 10.1038/ni.1695 19136960

상세보기
54 Al-Shami A Spolski R Kelly J 2004 A role for thymic stromal lymphopoietin in CD4(+) T cell development J Exp Med 200 159 168 10.1084/jem.20031975 15263024

상세보기
55 Peschon JJ Morrissey PJ Grabstein KH 1994 Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice J Exp Med 180 1955 1960 10.1084/jem.180.5.1955 7964471

상세보기
56 von Freeden-Jeffry U Vieira P Lucian LA McNeil T Burdach SE Murray R 1995 Lymphopenia in interleukin (IL)-7 gene-deleted mice identifies IL-7 as a nonredundant cytokine J Exp Med 181 1519 1526 10.1084/jem.181.4.1519 7699333

상세보기
57 Clark MR Mandal M Ochiai K Singh H 2014 Orchestrating B cell lymphopoiesis through interplay of IL-7 receptor and pre-B cell receptor signalling Nat Rev Immunol 14 69 80 10.1038/nri3570 24378843

상세보기
58 Puel A Ziegler SF Buckley RH Leonard WJ 1998 Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency Nat Genet 20 394 397 10.1038/3877 9843216

상세보기
59 Mazzucchelli R Durum SK 2007 Interleukin-7 receptor expression: intelligent design Nat Rev Immunol 7 144 154 10.1038/nri2023 17259970

상세보기
60 Kondo M Akashi K Domen J Sugamura K Weissman IL 1997 Bcl-2 rescues T lymphopoiesis, but not B or NK cell development, in common gamma chain-deficient mice Immunity 7 155 162 10.1016/S1074-7613(00)80518-X 9252128

상세보기
61 Akashi K Kondo M von Freeden-Jeffry U Murray R Weissman IL 1997 Bcl-2 rescues T lymphopoiesis in interleukin-7 receptor-deficient mice Cell 89 1033 1041 10.1016/S0092-8674(00)80291-3 9215626

상세보기
62 Maraskovsky E O'Reilly LA Teepe M Corcoran LM Peschon JJ Strasser A 1997 Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-1(-/-) mice Cell 89 1011 1019 10.1016/S0092-8674(00)80289-5 9215624

상세보기
63 Pellegrini M Bouillet P Robati M Belz GT Davey GM Strasser A 2004 Loss of Bim increases T cell production and function in interleukin 7 receptor-deficient mice J Exp Med 200 1189 1195 10.1084/jem.20041328 15504823

상세보기
64 Khaled AR Li WQ Huang J 2002 Bax deficiency partially corrects interleukin-7 receptor alpha deficiency Immunity 17 561 573 10.1016/S1074-7613(02)00450-8 12433363

상세보기
65 Boudil A Matei IR Shih HY 2015 IL-7 coordinates proliferation, differentiation and Tcra recombination during thymocyte beta-selection Nat Immunol 16 397 405 10.1038/ni.3122 25729925

상세보기
66 Moore TA von Freeden-Jeffry U Murray R Zlotnik A 1996 Inhibition of gamma delta T cell development and early thymocyte maturation in IL-7 -/- mice J Immunol 157 2366 2373 8805634

상세보기
67 Shitara S Hara T Liang B 2013 IL-7 produced by thymic epithelial cells plays a major role in the development of thymocytes and TCRgammadelta+ intraepithelial lymphocytes J Immunol 190 6173 6179 10.4049/jimmunol.1202573 23686483

상세보기
68 Vosshenrich CA Garcia-Ojeda ME Samson-Villeger SI 2006 A thymic pathway of mouse natural killer cell development characterized by expression of GATA-3 and CD127 Nat Immunol 7 1217 1224 10.1038/ni1395 17013389

상세보기
69 Vogt TK Link A Perrin J Finke D Luther SA 2009 Novel function for interleukin-7 in dendritic cell development Blood 113 3961 3968 10.1182/blood-2008-08-176321 19246338

상세보기
70 Soares MV Borthwick NJ Maini MK Janossy G Salmon M Akbar AN 1998 IL-7-dependent extrathymic expansion of CD45RA+ T cells enables preservation of a naive repertoire J Immunol 161 5909 5917 9834071

상세보기
71 Swainson L Kinet S Mongellaz C Sourisseau M Henriques T Taylor N 2007 IL-7-induced proliferation of recent thymic emigrants requires activation of the PI3K pathway Blood 109 1034 1042 10.1182/blood-2006-06-027912 17023582

상세보기
72 Ernst B Lee DS Chang JM Sprent J Surh CD 1999 The peptide ligands mediating positive selection in the thymus control T cell survival and homeostatic proliferation in the periphery Immunity 11 173 181 10.1016/S1074-7613(00)80092-8 10485652

상세보기
73 Goldrath AW Bevan MJ 1999 Low-affinity ligands for the TCR drive proliferation of mature CD8+ T cells in lymphopenic hosts Immunity 11 183 190 10.1016/S1074-7613(00)80093-X 10485653

상세보기
74 Surh CD Sprent J 2008 Homeostasis of naive and memory T cells Immunity 29 848 862 10.1016/j.immuni.2008.11.002 19100699

상세보기
75 Surh CD Sprent J 2005 Regulation of mature T cell homeostasis Semin Immunol 17 183 191 10.1016/j.smim.2005.02.007 15826823

상세보기
76 Hennion-Tscheltzoff O Leboeuf D Gauthier SD 2013 TCR triggering modulates the responsiveness and homeostatic proliferation of CD4+ thymic emigrants to IL-7 therapy Blood 121 4684 4693 10.1182/blood-2012-09-458174 23613523

상세보기
77 Park JH Adoro S Lucas PJ 2007 'Coreceptor tuning': cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR Nat Immunol 8 1049 1059 10.1038/ni1512 17873878

상세보기
78 Seddiki N Santner-Nanan B Martinson J 2006 Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells J Exp Med 203 1693 1700 10.1084/jem.20060468 16818676

상세보기
79 Liu W Putnam AL Xu-Yu Z 2006 CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells J Exp Med 203 1701 1711 10.1084/jem.20060772 16818678

상세보기
80 Barata JT Silva A Brandao JG Nadler LM Cardoso AA Boussiotis VA 2004 Activation of PI3K is indispensable for interleukin 7-mediated viability, proliferation, glucose use, and growth of T cell acute lymphoblastic leukemia cells J Exp Med 200 659 669 10.1084/jem.20040789 15353558

상세보기
81 Wofford JA Wieman HL Jacobs SR Zhao Y Rathmell JC 2008 IL-7 promotes Glut1 trafficking and glucose uptake via STAT5-mediated activation of Akt to support T-cell survival Blood 111 2101 2111 10.1182/blood-2007-06-096297 18042802

상세보기
82 Cui GL Staron MM Gray SM 2015 IL-7-induced glycerol transport and TAG synthesis promotes memory CD8(+) T cell longevity Cell 161 750 761 10.1016/j.cell.2015.03.021 25957683

상세보기
83 Kimura MY Pobezinsky LA Guinter TI 2013 IL-7 signaling must be intermittent, not continuous, during CD8 (+) T cell homeostasis to promote cell survival instead of cell death Nat Immunol 14 143 151 10.1038/ni.2494 23242416

상세보기
84 Rosenberg SA Sportes C Ahmadzadeh M 2006 IL-7 administration to humans leads to expansion of CD8 + and CD4 + cells but a relative decrease of CD4 + T-regulatory cells J Immunother 29 313 319 10.1097/01.cji.0000210386.55951.c2 16699374

상세보기
85 Sportes C Hakim FT Memon SA 2008 Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets J Exp Med 205 1701 1714 10.1084/jem.20071681 18573906

상세보기
86 Tredan O Menetrier-Caux C Ray-Coquard I 2015 ELYPSE-7: a randomized placebo-controlled phase IIa trial with CYT107 exploring the restoration of CD4 + lymphocyte count in lymphopenic metastatic breast cancer patients Ann Oncol 26 1353 1362 10.1093/annonc/mdv173 25851629

상세보기
87 Merchant MS Bernstein D Amoako M 2016 Adjuvant immunotherapy to improve outcome in high-risk pediatric sarcomas Clin Cancer Res 22 3182 3191 10.1158/1078-0432.CCR-15-2550 26823601

상세보기
88 Reimers MA Slane KE Pachynski RK 2019 Immunotherapy in metastatic castration-resistant prostate cancer: past and future strategies for optimization Curr Urol Rep 20 64 10.1007/s11934-019-0931-3 31482315

상세보기
89 Sportes C Babb RR Krumlauf MC 2010 Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy Clin Cancer Re-s 16 727 735 10.1158/1078-0432.CCR-09-1303 20068111

상세보기
90 Miller PW Sharma S Stolina M 2000 Intratumoral administration of adenoviral interleukin 7 gene-modified dendritic cells augments specific antitumor immunity and achieves tumor eradication Hum Gene Ther 11 53 65 10.1089/10430340050016157 10646639

상세보기
91 Li B VanRoey MJ Jooss K 2007 Recombinant IL-7 enhances the potency of GM-CSF-secreting tumor cell immunotherapy Clin Immunol 123 155 165 10.1016/j.clim.2007.01.002 17320482

상세보기
92 Pellegrini M Calzascia T Elford AR 2009 Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies Nat Med 15 528 536 10.1038/nm.1953 19396174

상세보기
93 Andersson A ivastava MK Sr Harris-White M 2011 Role of CXCR3 ligands in IL-7/IL-7R alpha-Fc-mediated antitumor activity in lung cancer Clin Cancer Res 17 3660 3672 10.1158/1078-0432.CCR-10-3346 21636553

상세보기
94 Boyman O Ramsey C Kim DM Sprent J Surh CD 2008 IL-7/anti-IL-7 mAb complexes restore T cell development and induce homeostatic T cell expansion without lymphopenia J Immunol 180 7265 7275 10.4049/jimmunol.180.11.7265 18490726

상세보기
95 Martin CE van Leeuwen EM Im SJ Roopenian DC Sung YC Surh CD 2013 IL-7/anti-IL-7 mAb complexes augment cytokine potency in mice through association with IgG-Fc and by competition with IL-7R Blood 121 4484 4492 10.1182/blood-2012-08-449215 23610371

상세보기
96 Nam HJ Song MY Choi DH Yang SH Jin HT Sung YC 2010 Marked enhancement of antigen-specific T-cell responses by IL-7-fused nonlytic, but not lytic, Fc as a genetic adjuvant Eur J Immunol 40 351 358 10.1002/eji.200939271 19950168

상세보기
97 Lee SW Choi D Heo M 2020 hIL-7-hyFc, a long-acting IL-7, increased absolute lymphocyte count in healthy subjects Clin Transl Sci 13 1161 1169 10.1111/cts.12800 32339447

상세보기
98 Choi YW Kang MC Seo YB 2016 Intravaginal administration of Fc-fused IL7 suppresses the cervicovaginal tumor by recruiting HPV DNA vaccine-induced CD8 T cells Clin Cancer Res 22 5898 5908 10.1158/1078-0432.CCR-16-0423 27407095

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99 Kim JH Kim YM Choi D 2020 Hybrid Fc-fused interleukin-7 induces an inflamed tumor microenvironment and improves the efficacy of cancer immunotherapy Clin Transl Immunology 9 e1168 10.1002/cti2.1168 32994996

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표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

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구성항목	기본정보 상세정보 관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관 관리번호, 논문명, 대등논문명, 저자 , 저널/프로시딩명, 발행기관, 발행년, 발행언어, 권, 호, 시작페이지, 끝페이지, ISBN, ISSN, 주제분야, 키워드, 초록(한글), 초록(영문), 저자(소속기관)
저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
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