Chronic lymphocytic leukemia cells induce defective LFA-1-directed T-cell motility by altering Rho GTPase signaling that is reversible with lenalidomide

Blood

Volumn 121, Issue 14, 2013, Pages 2704-2714

  Ramsay, Alan G ^a   Evans, Rachel ^a   Kiaii, Shahryar ^a   Svensson, Lena ^b   Hogg, Nancy ^b   Gribben, John G ^a  

^a QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^b IMPERIAL CANCER RESEARCH FUND   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

APC PROTEIN; CHEMOKINE RECEPTOR CCR7; CHEMOKINE RECEPTOR CXCR4; INTERCELLULAR ADHESION MOLECULE 1; LENALIDOMIDE; LYMPHOCYTE FUNCTION ASSOCIATED ANTIGEN 1; PROTEIN CDC42; PROTEIN KINASE ZAP 70; RAC1 PROTEIN; RHO GUANINE NUCLEOTIDE BINDING PROTEIN; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN; STROMAL CELL DERIVED FACTOR 1; ANTINEOPLASTIC AGENT; CRBN PROTEIN, HUMAN; DRUG DERIVATIVE; IMMUNOLOGIC FACTOR; PEPTIDE HYDROLASE; RAC1 PROTEIN, HUMAN; RHOA PROTEIN, HUMAN; THALIDOMIDE;

ARTICLE; CANCER PATIENT; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL ADHESION; CELL CONTACT; CHRONIC LYMPHATIC LEUKEMIA; COCULTURE; COMPARATIVE STUDY; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFECT; ENZYME ACTIVATION; GENE EXPRESSION; HUMAN; HUMAN CELL; IMMUNE EVASION; IMMUNOMODULATION; LEUKEMIA CELL LINE; LEUKEMOGENESIS; LYMPHOCYTE MIGRATION; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; TUMOR CELL; UPREGULATION; CELL MOTION; CYTOLOGY; IMMUNOLOGY; METABOLISM; PATHOLOGY; PRIMARY CELL CULTURE; T LYMPHOCYTE; TUMOR CELL CULTURE;

ANTINEOPLASTIC AGENTS; CDC42 GTP-BINDING PROTEIN; CELL MOVEMENT; COCULTURE TECHNIQUES; HUMANS; IMMUNOLOGIC FACTORS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1; PEPTIDE HYDROLASES; PRIMARY CELL CULTURE; RAC1 GTP-BINDING PROTEIN; RHO GTP-BINDING PROTEINS; RHOA GTP-BINDING PROTEIN; SIGNAL TRANSDUCTION; T-LYMPHOCYTES; THALIDOMIDE; TUMOR CELLS, CULTURED;

MLCS; MLOWN;

EID: 84878263355     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2012-08-448332     Document Type: Article

References (44)

1. Smith A, Stanley P, Jones K, et al. The role of the integrin LFA-1 in T-lymphocyte migration. Immunol Rev. 2007;218:135-146.
2. Springer TA, Dustin ML. Integrin inside-out signaling and the immunological synapse. Curr Opin Cell Biol. 2012;24(1):107-115.
3. Shamri R, Grabovsky V, Gauguet JM, et al. Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokines. Nat Immunol. 2005;6(5):497-506.
4. Hogg N, Patzak I, Willenbrock F. The insider's guide to leukocyte integrin signalling and function. Nat Rev Immunol. 2011;11(6):416-426.
5. Arnaout MA, Mahalingam B, Xiong JP. Integrin structure, allostery, and bidirectional signaling. Annu Rev Cell Dev Biol. 2005;21:381-410.
6. Billadeau DD, Nolz JC, Gomez TS. Regulation of T-cell activation by the cytoskeleton. Nat Rev Immunol. 2007;7(2):131-143.
7. Evans R, Patzak I, Svensson L, et al. Integrins in immunity. J Cell Sci. 2009;122(Pt 2):215-225.
8. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674.
9. Mellman I, Coukos G, Dranoff G. Cancer immunotherapy comes of age. Nature. 2011; 480(7378):480-489.
10. Zenz T, Mertens D, Küppers R, et al. From pathogenesis to treatment of chronic lymphocytic leukaemia. Nat Rev Cancer. 2010;10(1):37-50.
11. Lanasa MC. Novel insights into the biology of CLL. Hematology Am Soc Hematol Educ Program. 2010;2010:70-76.
12. Görgün G, Holderried TA, Zahrieh D, et al. Chronic lymphocytic leukemia cells induce changes in gene expression of CD4 and CD8 T cells. J Clin Invest. 2005;115(7):1797-1805.
13. Ramsay AG, Johnson AJ, Lee AM, et al. Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug. J Clin Invest. 2008;118(7):2427-2437.
14. Sims TN, Dustin ML. The immunological synapse: integrins take the stage. Immunol Rev. 2002;186: 100-117.
15. Ramsay AG, Clear AJ, Fatah R, et al. Multiple inhibitory ligands induce impaired T-cell immunologic synapse function in chronic lymphocytic leukemia that can be blocked with lenalidomide: establishing a reversible immune evasion mechanism in human cancer. Blood. 2012;120(7):1412-1421.
16. Wendtner CM, Hillmen P, Mahadevan D, et al. Final results of a multicenter phase 1 study of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia. Leuk Lymphoma. 2012;53(3):417-423.
17. Dransfield I, Cabañas C, Barrett J, et al. Interaction of leukocyte integrins with ligand is necessary but not sufficient for function. J Cell Biol. 1992;116(6):1527-1535.
18. Smith A, Carrasco YR, Stanley P, et al. A talindependent LFA-1 focal zone is formed by rapidly migrating T lymphocytes. J Cell Biol. 2005;170(1): 141-151.
19. Cernuda-Morollón E, Millán J, Shipman M, et al. Rac activation by the T-cell receptor inhibits T cell migration. PLoS ONE. 2010;5(8):e12393.
20. Smith A, Bracke M, Leitinger B, et al. LFA-1- induced T cell migration on ICAM-1 involves regulation of MLCK-mediated attachment and ROCK-dependent detachment. J Cell Sci. 2003; 116(Pt 15):3123-3133.
21. Svensson L, Howarth K, McDowall A, et al. Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activation. Nat Med. 2009;15(3):306-312.
22. Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med. 2005; 352(8):804-815.
23. Kay NE, O'Brien SM, Pettitt AR, et al. The role of prognostic factors in assessing 'high-risk' subgroups of patients with chronic lymphocytic leukemia. Leukemia. 2007;21(9):1885-1891.
24. Borge M, Nannini PR, Galletti JG, et al. CXCL12- induced chemotaxis is impaired in T cells from patients with ZAP-70-negative chronic lymphocytic leukemia. Haematologica. 2010; 95(5):768-775.
25. Chen CI, Bergsagel PL, Paul H, et al. Singleagent lenalidomide in the treatment of previously untreated chronic lymphocytic leukemia. J Clin Oncol. 2011;29(9):1175-1181.
26. Nowakowski GS, LaPlant B, Habermann TM, et al. Lenalidomide can be safely combined with R-CHOP (R2CHOP) in the initial chemotherapy for aggressive B-cell lymphomas: phase I study. Leukemia. 2011;25(12):1877-1881.
27. Ramsay AG, Gribben JG. Immune dysfunction in chronic lymphocytic leukemia T cells and lenalidomide as an immunomodulatory drug. Haematologica. 2009;94(9):1198-1202.
28. Lopez-Girona A, Mendy D, Ito T, et al. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia. 2012;26(11): 2326-2335.
29. Takagi J, Springer TA. Integrin activation and structural rearrangement. Immunol Rev. 2002; 186:141-163.
30. Tybulewicz VL, Henderson RB. Rho family GTPases and their regulators in lymphocytes. Nat Rev Immunol. 2009;9(9):630-644.
31. Rougerie P, Delon J. Rho GTPases: masters of T lymphocyte migration and activation. Immunol Lett. 2012;142(1-2):1-13.
32. Shanafelt TD, Tun H, Hanson CA, et al. Lenalidomide consolidation appears to prolong time to retreatment after first-line chemoimmunotherapy for patients with previously untreated CLL. Blood (ASH Annual ASH Meeting Abstracts). 2011;118:3899.
33. Bolomini-Vittori M, Montresor A, Giagulli C, et al. Regulation of conformer-specific activation of the integrin LFA-1 by a chemokine-triggered Rho signaling module. Nat Immunol. 2009;10(2): 185-194.
34. Giagulli C, Scarpini E, Ottoboni L, et al. RhoA and zeta PKC control distinct modalities of LFA-1 activation by chemokines: critical role of LFA-1 affinity triggering in lymphocyte in vivo homing. Immunity. 2004;20(1):25-35.
35. Heasman SJ, Carlin LM, Cox S, et al. Coordinated RhoA signaling at the leading edge and uropod is required for T cell transendothelial migration. J Cell Biol. 2010;190(4):553-563.
36. D'Souza-Schorey C, Boettner B, Van Aelst L. Rac regulates integrin-mediated spreading and increased adhesion of T lymphocytes. Mol Cell Biol. 1998;18(7):3936-3946.
37. Ratner S, Piechocki MP, Galy A. Role of Rhofamily GTPase Cdc42 in polarized expression of lymphocyte appendages. J Leukoc Biol. 2003; 73(6):830-840.
38. Morin NA, Oakes PW, Hyun YM, et al. Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration. J Exp Med. 2008;205(1): 195-205.
39. published correction appears in J Exp Med. 2008;205(4):993.
40. Gorgun G, Ramsay AG, Holderried TA, et al. E(mu)-TCL1 mice represent a model for immunotherapeutic reversal of chronic lymphocytic leukemia-induced T-cell dysfunction. Proc Natl Acad Sci USA. 2009;106(15): 6250-6255.
41. Ghandour H, Cullere X, Alvarez A, et al. Essential role for Rap1 GTPase and its guanine exchange factor CalDAG-GEFI in LFA-1 but not VLA-4 integrin mediated human T-cell adhesion. Blood. 2007;110(10): 3682-3690.
42. Schürpf T, Springer TA. Regulation of integrin affinity on cell surfaces. EMBO J. 2011;30(23): 4712-4727.
43. Evans R, Lellouch AC, Svensson L, et al. The integrin LFA-1 signals through ZAP-70 to regulate expression of high-affinity LFA-1 on T lymphocytes. Blood. 2011;117(12): 3331-3342.
44. Zhu J, Luo BH, Xiao T, et al. Structure of a complete integrin ectodomain in a physiologic resting state and activation and deactivation by applied forces. Mol Cell. 2008; 32(6):849-861.