Evaluation of intracellular signaling downstream chimeric antigen receptors

PLoS ONE

Volumn 10, Issue 12, 2015, Pages

  Karlsson, Hannah ^a   Svensson, Emma ^a   Gigg, Camilla ^a   Jarvius, Malin ^a   Olsson Strömberg, Ulla ^a,b   Savoldo, Barbara ^c   Dotti, Gianpietro ^c   Loskog, Angelica ^a  

^a UPPSALA UNIVERSITY   (Sweden)

^b UPPSALA UNIVERSITY HOSPITAL   (Sweden)

^c CENTER FOR CELL AND GENE THERAPY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHIMERIC ANTIGEN RECEPTOR; INTERLEUKIN 2; CD137 ANTIGEN; CD28 ANTIGEN; LYMPHOCYTE ANTIGEN RECEPTOR; TNFRSF9 PROTEIN, HUMAN;

ARTICLE; B LYMPHOCYTE; BIOACCUMULATION; CELL ADHESION; CELL CYCLE; CELL EXPANSION; CONTROLLED STUDY; CYTOTOXICITY; ENZYME ACTIVATION; EXOCYTOSIS; HUMAN; HUMAN CELL; IMMUNOSTIMULATION; IN VIVO STUDY; INTRACELLULAR SIGNALING; LYMPHOCYTE PROLIFERATION; MOUSE; NONHUMAN; PROTEIN PHOSPHORYLATION; T LYMPHOCYTE; ANIMAL; C57BL MOUSE; CASE CONTROL STUDY; COMPARATIVE STUDY; CYTOTOXIC T LYMPHOCYTE; EVALUATION STUDY; FLOW CYTOMETRY; IMMUNOLOGY; IMMUNOTHERAPY; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; LYMPHOCYTE ACTIVATION; NORMAL HUMAN; NUDE MOUSE; PATHOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; ANTIGENS, CD137; ANTIGENS, CD28; CASE-CONTROL STUDIES; FLOW CYTOMETRY; HEALTHY VOLUNTEERS; HUMANS; IMMUNOTHERAPY; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; LYMPHOCYTE ACTIVATION; MICE; MICE, INBRED C57BL; MICE, NUDE; RECEPTORS, ANTIGEN; SIGNAL TRANSDUCTION; T-LYMPHOCYTES, CYTOTOXIC;

EID: 84956906467     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0144787     Document Type: Article

References (67)

1. Brentjens RJ, Davila ML, Riviere I, Park J., Wang X, Cowell LG, et al CD19-targetedT cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med. 2013; 5(177):177ra38. Epub 2013/03/22. doi:10.1126/scitranslmed.30059305/177/177ra38 [pii]. PMID: 23515080; PubMed Central PMCID: PMC3742551.
2. Kalos M, Levine BL, Porter D.L., Katz S., Grupp SA, Bagg A, et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011; 3(95):95ra73. Epub 2011/08/13. doi: 3/95/95ra73 [pii] doi: 10.1126/scitranslmed.3002842 PMID: 21832238.
3. Grupp SA, Kalos M, Barrett D., Aplenc R, Porter DL, Rheingold S.R., et al. Chimeric antigen receptormodified T cells for acute lymphoid leukemia. N Engl J Med. 2013; 368(16):1509-18. Epub 2013/03/27. doi:10.1056/NEJMoa1215134 PMID: 23527958.
4. Kochenderfer JN, Dudley ME, Kassim S.H., Somerville RP, Carpenter RO, Stetler-Stevenson M, et al. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. J Clin Oncol. 2015; 33(6):540-9. doi:10.1200/JCO.2014.56.2025 PMID: 25154820; PubMed Central PMCID: PMC4322257.
5. Davila ML, Riviere I, Wang X., Bartido S, Park J, Curran K., et al. Efficacy and toxicity management of 19-28z CART cell therapy in Bcell acute lymphoblastic leukemia. Sci Transl Med. 2014; 6 (224): 224ra25. Epub 2014/02/21. doi:10.1126/scitranslmed.30082266/224/224ra25 [pii]. PMID: 24553386.
6. Eshhar Z, Waks T, Gross G., Schindler DG. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc Natl Acad Sci USA. 1993; 90(2):720-4. Epub 1993/ 01/15. PMID: 8421711; PubMed Central PMCID: PMC45737.
7. Kershaw MH, Westwood JA, Parker L.L., Wang G., Eshhar Z, Mavroukakis SA, et al A phase I study on adoptive immunotherapy using gene-modified T cells for ovarian cancer. Clin Cancer Res. 2006; 12(20 Pt 1):6106-15. Epub 2006/10/26. doi: 12/20/6106 [pii] doi: 10.1158/1078-0432.CCR-06-1183 PMID: 17062687; PubMed Central PMCID: PMC2154351.
8. Lamers CH, Sleijfer S, Vulto A.G., Kruit WH, Kliffen M, Debets R, et al Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience. J Clin Oncol. 2006; 24(13):e20-2. Epub 2006/05/02. doi: 24/13/e20 [pii] doi: 10.1200/JCO.2006.05.9964 PMID: 16648493.
9. Till BG, Jensen MC, Wang J, Chen E.Y., Wood BL, Greisman HA, et al. Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specificT cells. Blood. 2008; 112(6):2261-71. Epub 2008/05/30. doi:10.1182/blood-2007-12-128843 [pii]. PMID: 18509084; PubMed Central PMCID: PMC2532803.
10. Loskog A, Giandomenico V, Rossig C., Pule M, Dotti G, Brenner MK Addition of the CD28 signaling domain to chimeric T-cell receptors enhances chimeric T-cell resistance to T regulatory cells. Leukemia. 2006; 20(10):1819-28. Epub 2006/08/26. doi:2404366 [pii] doi: 10.1038/sj.leu.2404366 PMID: 16932339.
11. Savoldo B, Ramos CA, Liu E, Mims M.P., Keating MJ, Carrum G, et al. CD28 costimulation improves expansion and persistence of chimeric antigen receptor-modified T cells in lymphoma patients. J Clin Invest. 2011; 121(5):1822-6. Epub 2011/05/05. doi:10.1172/JCI4611046110 [pii]. PMID: 21540550; PubMed Central PMCID: PMC3083795.
12. Wang J, Jensen M, Lin Y., Sui X, Chen E, Lindgren C.G., et al. Optimizing adoptive polyclonal T cell immunotherapy of lymphomas, using a chimeric T cell receptor possessing CD28 and CD137 costimulatory domains. Hum Gene Ther. 2007; 18(8):712-25. Epub 2007/08/10. doi:10.1089/hum.2007.028 PMID: 17685852.
13. Maher J, Brentjens RJ, Gunset G, Riviere I., Sadelain M. Human T-lymphocyte cytotoxicity and proliferation directed by a single chimeric TCRzeta/CD28 receptor. Nat Biotechnol. 2002; 20(1):70-5. doi:10.1038/nbt0102-70 PMID: 11753365.
14. Finney HM, Akbar AN, Lawson AD Activation of resting human primary T cells with chimeric receptors: costimulation from CD28, inducible costimulator, CD134, and CD137 in series with signals from the TCRzeta chain. J Immunol. 2004; 172(1):104-13. Epub 2003/12/23. PMID: 14688315.
15. Vera J, Savoldo B, Vigouroux S., Biagi E, Pule M, Rossig C., et al. Tlymphocytes redirected against the kappa light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells. Blood. 2006; 108(12):3890-7. doi:10.1182/blood-2006-04-017061 PMID: 16926291; PubMed Central PMCID: PMCPMC1895462.
16. Kowolik CM, Topp MS, Gonzalez S, Pfeiffer T., Olivares S, Gonzalez N, et al CD28 costimulation provided through a CD19-specific chimeric antigen receptor enhances in vivo persistence and antitumor efficacy of adoptively transferred T cells. Cancer Res. 2006; 66(22):10995-1004. Epub 2006/11/17. doi:66/22/10995 [pii] doi: 10.1158/0008-5472.CAN-06-0160 PMID: 17108138.
17. Imai C, Mihara K, Andreansky M., Nicholson IC, Pui CH, Geiger TL, et al Chimeric receptors with 4-1BB signaling capacity provoke potent cytotoxicity against acute lymphoblastic leukemia. Leukemia. 2004; 18(4):676-84. Epub 2004/02/13. doi:10.1038/sj.leu.24033022403302 [pii]. PMID: 14961035.
18. Tammana S, Huang X, Wong M., Milone MC, Ma L, Levine BL, et al 4-1BB and CD28 signaling plays a synergistic role in redirecting umbilical cord blood T cells against B-cell malignancies. Hum Gene Ther. 2010; 21(1):75-86. Epub 2009/09/02. doi:10.1089/hum.2009.122 PMID: 19719389; PubMed Central PMCID: PMC2861957.
19. Carpenito C, Milone MC, Hassan R, Simonet J.C., Lakhal M., Suhoski MM, et al. Control of large, established tumor xenografts with genetically retargeted human T cells containing CD28 and CD137 domains. Proc Natl Acad Sci USA. 2009; 106(9):3360-5. doi:10.1073/pnas.0813101106 PMID: 19211796; PubMed Central PMCID: PMCPMC2651342.
20. Pule MA, Straathof KC, Dotti G, Heslop H.E., Rooney CM, Brenner MK. A chimeric T cell antigen receptor that augments cytokine release and supports clonal expansion of primary human T cells. Mol Ther. 2005; 12(5):933-41. doi:10.1016/j.ymthe.2005.04.016 PMID: 15979412.
21. Hillerdal V, Ramachandran M, Leja J., Essand M. Systemic treatment with CAR-engineeredT cells against PSCA delays subcutaneous tumor growth and prolongs survival of mice. BMC Cancer. 2014; 14:30. doi:10.1186/1471-2407-14-30 PMID: 24438073; PubMed Central PMCID: PMCPMC3899402.
22. Santoro SP, Kim S, Motz G.T., Alatzoglou D., Li C, Irving M, et al T cells bearing a chimeric antigen receptor against prostate-specific membrane antigen mediate vascular disruption and result in tumor regression. Cancer immunology research. 2015; 3(1):68-84. doi:10.1158/2326-6066CIR-14-0192 PMID: 25358763; PubMed Central PMCID: PMCPMC4289112.
23. Abate-Daga D., Lagisetty KH, Tran E, Zheng Z., Gattinoni L, Yu Z, et al A novel chimeric antigen receptor against prostate stem cell antigen mediates tumor destruction in a humanized mouse model of pancreatic cancer. Hum Gene Ther. 2014; 25(12):1003-12. doi:10.1089/hum.2013.209 PMID: 24694017; PubMed Central PMCID: PMCPMC4270113.
24. Gao H, Li K, Tu H., Pan X, Jiang H, Shi B., et al. Development of T cells redirected to glypican-3 for the treatment of hepatocellular carcinoma. Clin Cancer Res. 2014; 20(24):6418-28. doi:10.1158/1078-0432.CCR-14-1170 PMID: 25320357.
25. Sampson JH, Choi BD, Sanchez-Perez L, Suryadevara C.M., Snyder DJ, Flores CT, et al. EGFRvIII mCAR-Modified T-Cell Therapy Cures Mice with Established Intracerebral Glioma and Generates Host Immunity against Tumor-Antigen Loss. Clinical Cancer Research. 2014; 20(4):972-84. doi: 10.1158/1078-0432.ccr-13-0709 PMID: 24352643
26. Till BG, Jensen MC, Wang J, Qian X., Gopal AK, Maloney DG, et al. CD20-specific adoptive immunotherapy for lymphoma using a chimeric antigen receptor with both CD28 and 4-1BB domains: pilot clinical trial results. Blood. 2012; 119(17):3940-50. Epub 2012/02/07. doi:blood-2011-10-387969 [pii] doi: 10.1182/blood-2011-10-387969 PMID: 22308288; PubMed Central PMCID: PMC3350361.
27. Milone MC, Fish JD, Carpenito C, Carroll R.G., Binder GK, Teachey D, et al. Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther. 2009; 17(8):1453-64. Epub 2009/04/23. doi:mt200983 [pii] doi: 10.1038/mt.2009.83 PMID: 19384291; PubMed Central PMCID: PMC2805264.
28. Maude SL, Teachey DT, Porter D.L., Grupp SA. CD19-targeted chimeric antigen receptorT cell therapy for acute lymphoblastic leukemia. Blood. 2015. doi:10.1182/blood-2014-12-580068 PMID: 25999455.
29. Maude SL, Frey N, Shaw P.A., Aplenc R., Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N EnglJ Med. 2014; 371(16):1507-17. doi:10.1056/NEJMoa1407222 PMID: 25317870; PubMed Central PMCID: PMC4267531.
30. Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui Y.K., Delbrook C., Feldman SA, et al. Tcells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015; 385(9967):517-28. doi:10.1016/S0140-6736(14)61403-3 PMID: 25319501.
31. Klein E, Klein G, Nadkarni J.S., Nadkarni JJ, Wigzell H, Clifford P. Surface IgM-kappa specificity on a Burkitt lymphoma cell in vivo and in derived culture lines. Cancer Res. 1968; 28(7):1300-10. Epub 1968/07/01. PMID: 4174339.
32. Nicholson IC, Lenton KA, Little D.J., Decorso T., Lee FT, Scott AM, et al. Construction and characterisation of afunctional CD19 specific single chain Fv fragment for immunotherapy of B lineage leukaemia and lymphoma. Mol Immunol. 1997; 34(16-17):1157-65. Epub 1998/05/05. PMID: 9566763.
33. Weissman AM, Hou D, Orloff D.G., Modi WS, Seuanez H, O'Brien SJ, et al. Molecular cloning and chromosomal localization of the human T-cell receptor zeta chain: distinction from the molecular CD3 complex. Proc Natl Acad Sci USA. 1988; 85(24):9709-13. Epub 1988/12/01. PMID: 2974162; PubMed Central PMCID: PMC282845.
34. Riviere I, Brose K, Mulligan RC Effects of retroviral vector design on expression of human adenosine deaminase in murine bone marrow transplant recipients engrafted with genetically modified cells. Proc Natl Acad Sci USA. 1995; 92(15):6733-7. Epub 1995/07/18. PMID: 7624312; PubMed Central PMCID: PMC41403.
35. Essand M, Loskog AS. Genetically engineered T cells for the treatment of cancer. J Intern Med. 2013; 273(2):166-81. Epub 2012/12/04. doi:10.1111/joim.12020 PMID: 23198862; PubMed Central PMCID: PMC3607417.
36. Smith-Garvin J.E., Koretzky GA, Jordan MS Tcell activation. Annu Rev Immunol. 2009; 27:591-619. Epub 2009/01/10. doi:10.1146/annurev.immunol.021908.132706 [pii]. PMID: 19132916; PubMed Central PMCID: PMC2740335.
37. Croft M. Co-stimulatory members of the TNFR family: keys to effective T-cell immunity? Nat Rev Immunol. 2003; 3(8):609-20. Epub 2003/09/17. doi:10.1038/nri1148nri1148 [pii]. PMID: 12974476.
38. Zhong XS, Matsushita M, Plotkin J., Riviere I, Sadelain M. Chimeric antigen receptors combining 4-1BB and CD28 signaling domains augment PI3kinase/AKT/Bcl-XL activation and CD8+ T cell-mediated tumor eradication. MolTher. 2010; 18(2):413-20. Epub 2009/09/24. doi:mt2009210 [pii] doi: 10.1038/mt.2009.210 PMID: 19773745; PubMed Central PMCID: PMC2839303.
39. Hombach AA, Chmielewski M, Rappl G., Abken H. Adoptive immunotherapy with redirected T cells produces CCR7-cells that are trapped in the periphery and benefit from combined CD28-OX40 costimulation. Hum Gene Ther. 2013; 24(3):259-69. Epub 2013/01/29. doi:10.1089/hum.2012.247 PMID: 23350854.
40. Pule MA, Savoldo B, Myers G.D., Rossig C., Russell HV, Dotti G, et al. Virus-specificT cells engineered to coexpress tumor-specific receptors: persistence and antitumor activity in individuals with neuroblastoma. Nature medicine. 2008; 14(11):1264-70. Epub 2008/11/04. doi:10.1038/nm.1882nm.1882 [pii]. PMID: 18978797; PubMed Central PMCID: PMC2749734.
41. Song DG, Ye Q, Poussin M., Harms GM, Figini M, Powell DJ Jr. CD27 costimulation augments the survival and antitumor activity of redirected human T cells in vivo. Blood. 2012; 119(3):696-706. Epub 2011/11/26. doi:10.1182/blood-2011-03-344275 [pii]. PMID: 22117050.
42. Berger C, Jensen MC, Lansdorp P.M., Gough M., Elliott C, Riddell SR. Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent Tcell memory in primates. J Clin Invest. 2008; 118(1):294-305. Epub 2007/12/07. doi:10.1172/JCI32103 PMID: 18060041; PubMed Central PMCID: PMC2104476.
43. Hinrichs CS, Borman ZA, Cassard L, Gattinoni L., Spolski R, Yu Z, et al Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity. Proc Natl Acad Sci USA. 2009; 106(41):17469-74. Epub 2009/10/07. doi:10.1073/pnas. 09074481060907448106 [pii]. PMID: 19805141; PubMed Central PMCID: PMC2762661.
44. Gattinoni L, Lugli E, Ji Y., Pos Z, Paulos CM, Quigley M.F., et al. A human memory Tcell subset with stem cell-like properties. Nature medicine. 2011; 17(10):1290-7. Epub 2011/09/20. doi:10.1038/nm. 2446nm.2446 [pii]. PMID: 21926977; PubMed Central PMCID: PMC3192229.
45. Xu Y, Zhang M, Ramos C.A., Durett A., Liu E, Dakhova O, et al Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7and IL-15. Blood. 2014; 123(24):3750-9. Epub 2014/05/02. doi:10.1182/blood-2014-01-552174 [pii]. PMID: 24782509; PubMed Central PMCID: PMC4055922.
46. Singh H, Figliola MJ, Dawson M.J., Olivares S., Zhang L, Yang G, et al Manufacture of clinical-grade CD19-specific T cells stably expressing chimeric antigen receptor using Sleeping Beauty system and artificial antigen presenting cells. PLoSOne. 2013; 8(5): e64138. Epub 2013/06/07. doi:10.1371/journal.pone.0064138PONE-D-13-04181 [pii]. PMID: 23741305; PubMed Central PMCID: PMC3669363.
47. Barrett DM, Singh N, Liu X., Jiang S, June CH, Grupp S.A., et al. Relation of clinical culture method to T-cell memory status and efficacy in xenograft models of adoptive immunotherapy. Cytotherapy. 2014; 16(5):619-30. Epub 2014/01/21. doi:10.1016/j.jcyt.2013.10.013S1465-3249(13)00759-7 [pii]. PMID: 24439255; PubMed Central PMCID: PMC3988256.
48. Hudecek M, Sommermeyer D, Kosasih P.L., Silva-Benedict A, Liu L, Rader C., et al. The non-signaling extracellular spacer domain of chimeric antigen receptors is decisive for in vivo antitumor activity. Cancer immunology research. 2014. doi:10.1158/2326-6066.CIR-14-0127 PMID: 25212991.
49. Liu JO. Calmodulin-dependent phosphatase, kinases, and transcriptional corepressors involved in T-cell activation. Immunol Rev. 2009; 228(1):184-98. Epub 2009/03/18. doi:10.1111/j.1600-065X.2008. 00756.xIMR756 [pii]. PMID: 19290928; PubMed Central PMCID: PMC2669740.
50. Gerke V, Creutz CE, Moss SE Annexins: linking Ca2+ signalling to membrane dynamics. Nat Rev Mol Cell Biol. 2005; 6(6):449-61. Epub 2005/06/02. doi:nrm1661 [pii] doi: 10.1038/nrm1661 PMID: 15928709.
51. van Genderen H.O., Kenis H, Hofstra L., Narula J, Reutelingsperger CP. Extracellular annexin A5: functions of phosphatidylserine-binding and two-dimensional crystallization. Biochim Biophys Acta. 2008; 1783(6):953-63. Epub 2008/03/13. doi:10.1016/j.bbamcr.2008.01.030S0167-4889(08)00044-X [pii]. PMID: 18334229.
52. Perretti M D'Acquisto F. Annexin A1 and glucocorticoids as effectors of the resolution of inflammation. Nat Rev Immunol. 2009; 9(1):62-70. Epub 2008/12/24. doi:10.1038/nri2470nri2470 [pii]. PMID: 19104500.
53. Weyd H, Abeler-Dorner L, Linke B., Mahr A, Jahndel V, Pfrang S., et al. Annexin A1 on the surface of early apoptoticcells suppresses CD8+Tcell immunity. PLoSOne. 2013; 8(4):e62449. Epub 2013/05/03. doi:10.1371/journal.pone.0062449PONE-D-13-04100 [pii]. PMID: 23638088; PubMed Central PMCID: PMC3640057.
54. Dubois T, Oudinet JP, Russo-Marie F, Rothhut B. In vivo and in vitro phosphorylation of annexin II in T cells: potential regulation by annexin V. Biochem J. 1995; 310(Pt 1):243-8. Epub 1995/08/15. PMID: 7646452; PubMed Central PMCID: PMC1135879.
55. Chunder N, Wang L, Chen C., Hancock WW, Wells AD. Cyclin-dependent kinase 2 controls peripheral immune tolerance. J Immunol. 2012; 189(12):5659-66. Epub 2012/11/09. doi:10.4049/jimmunol. 1202313 [pii]. PMID: 23136201; PubMed Central PMCID: PMC3518671.
56. Morawski PA, Mehra P, Chen C., Bhatti T, Wells AD. Foxp3 protein stability is regulated by cyclindependent kinase 2. J Biol Chem. 2013; 288(34):24494-502. Epub 2013/07/16. doi:10.1074/jbc. M113.467704 [pii]. PMID: 23853094; PubMed Central PMCID: PMC3750148.
57. Gu H, Ding L, Xiong S.D., Gao XM, Zheng B. Inhibition of CDK2 promotes inducible regulatory T-cell differentiation through TGFbeta-Smad3 signaling pathway. Cell Immunol. 2014; 290(1):138-44. Epub 2014/07/01. doi:S0008-8749(14)00082-3 [pii] doi: 10.1016/j.cellimm.2014.05.004 PMID: 24978614.
58. Miao T, Raymond M, Bhullar P., Ghaffari E, Symonds AL, Meier U.C., et al. Early growth response gene-2 controls IL-17 expression and Th17 differentiation by negatively regulating Batf. J Immunol. 2013; 190(1):58-65. Epub 2012/12/04. doi:10.4049/jimmunol.1200868 [pii]. PMID: 23203924.
59. Austgen K, Johnson ET, Park T.J., Curran T., Oakes SA. The adaptor protein CRK is a pro-apoptotic transducer of endoplasmic reticulum stress. Nat Cell Biol. 2012; 14(1):87-92. Epub 2011/12/20. doi:10.1038/ncb2395ncb2395 [pii]. PMID: 22179045; PubMed Central PMCID: PMC3245775.
60. Kang Q, Yu Y, Pei X., Hughes R, Heck S, Zhang X., et al. Cytoskeletal protein 4.1R negatively regulates T-cell activation by inhibiting the phosphorylation of LAT. Blood. 2009; 113(24):6128-37. Epub 2009/ 02/05. doi:10.1182/blood-2008-10-182329 [pii]. PMID: 19190245; PubMed Central PMCID: PMC2699234.
61. Chapman NM, Connolly SF, Reinl E.L., Houtman JC. Focal adhesion kinase negatively regulates Lck function downstream of the T cell antigen receptor. J Immunol. 2013; 191(12):6208-21. Epub 2013/11/ 15. doi:10.4049/jimmunol.1301587 [pii]. PMID: 24227778; PubMed Central PMCID: PMC3865716.
62. Grebe C, Klingebiel TM, Grau S.P., Toischer K., Didie M, Jacobshagen C, et al Enhanced expression of DYRK1A in cardiomyocytes inhibits acute NFAT activation but does not prevent hypertrophy in vivo. Cardiovasc Res. 2011; 90(3):521-8. Epub 2011/01/29. doi:10.1093/cvr/cvr023cvr023 [pii]. PMID: 21273244.
63. Gwack Y, Sharma S, Nardone J., Tanasa B, Iuga A, Srikanth S., et al. Agenome-wide Drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT. Nature. 2006; 441(7093):646-50. Epub 2006/03/03. doi:nature04631 [pii] doi: 10.1038/nature04631 PMID: 16511445.
64. Lapinski PE, Qiao Y, Chang C.H., King PD. A role for p120 RasGAP in thymocyte positive selection and survival of naive T cells. J Immunol. 2011; 187(1):151-63. Epub 2011/06/08. doi:10.4049/jimmunol. 1100178 [pii]. PMID: 21646295; PubMed Central PMCID: PMC3119767.
65. Robertson LK, Ostergaard HL Paxillin associates with the microtubule cytoskeleton and the immunological synapse of CTL through its leucine-aspartic acid domains and contributes to microtubule organizing center reorientation. J Immunol. 2011; 187(11):5824-33. Epub 2011/11/02. doi:10.4049/jimmunol.1003690 [pii]. PMID: 22043013.
66. Proust R, Crouin C, Gandji L.Y., Bertoglio J., Gesbert F. The adaptor protein SAP directly associates with PECAM-1 and regulates PECAM-1-mediated-cell adhesion in T-like cell lines. Mol Immunol. 2014; 58 (2):206-13. Epub 2014/01/07. doi:10.1016/j.molimm.2013.12.002S0161-5890(13)00576-2 [pii]. PMID: 24388971.
67. Zaiss DM, van Loosdregt J, Gorlani A, Bekker C.P., Grone A., Sibilia M, et al. Amphiregulin enhances regulatory T cell-suppressive function via the epidermal growth factor receptor. Immunity. 2013; 38 (2):275-84. Epub 2013/01/22. doi:10.1016/j.immuni.2012.09.023S1074-7613(13)00002-2 [pii]. PMID: 23333074; PubMed Central PMCID: PMC3582723.