Increased T Regulatory Cells Are Associated with Adverse Clinical Features and Predict Progression in Multiple Myeloma

PLoS ONE

Volumn 7, Issue 10, 2012, Pages

  Muthu Raja, Karthick Raja ^a   Rihova, Lucie ^a   Zahradova, Lenka ^b   Klincova, Maria ^b   Penka, Miroslav ^a   Hajek, Roman ^a,b  

^a MASARYK UNIVERSITY   (Czech Republic)

^b UNIVERSITY HOSPITAL BRNO   (Czech Republic)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOPHOSPHAMIDE; DEXAMETHASONE; THALIDOMIDE;

ADULT; AGED; ARTICLE; AUTOLOGOUS STEM CELL TRANSPLANTATION; CANCER GROWTH; CANCER RECURRENCE; CD4+ T LYMPHOCYTE; CLINICAL FEATURE; COHORT ANALYSIS; CONTROLLED STUDY; FEMALE; FLOW CYTOMETRY; HUMAN; HYPERCALCEMIA; IMMUNE DEFICIENCY; LYMPHOCYTE ACTIVATION; LYMPHOCYTE FUNCTION; MAJOR CLINICAL STUDY; MALE; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; PLASMA CELL; PROGNOSIS; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION;

ADULT; AGED; AGED, 80 AND OVER; CASE-CONTROL STUDIES; CD4-POSITIVE T-LYMPHOCYTES; CYCLOPHOSPHAMIDE; DEXAMETHASONE; DISEASE PROGRESSION; FEMALE; HUMANS; HYPERCALCEMIA; MALE; MIDDLE AGED; MULTIPLE MYELOMA; PREDICTIVE VALUE OF TESTS; PROPORTIONAL HAZARDS MODELS; REFERENCE VALUES; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES, REGULATORY; THALIDOMIDE;

EID: 84867372743     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0047077     Document Type: Article

References (49)

1. Kyle RA, Rajkumar SV, (2009) Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma. Leukemia 23: 3-9.
2. Raja KR, Kovarova L, Hajek R, (2010) Review of phenotypic markers used in flow cytometric analysis of MGUS and MM, and applicability of flow cytometry in other plasma cell disorders. Br J Haematol 149: 334-351.
3. Pratt G, Goodyear O, Moss P, (2007) Immunodeficiency and immunotherapy in multiple myeloma. Br J Haematol 138: 563-579.
4. Kay NE, Leong TL, Bone N, Vesole DH, Greipp PR, et al. (2001) Blood levels of immune cells predict survival in myeloma patients: results of an Eastern Cooperative Oncology Group phase 3 trial for newly diagnosed multiple myeloma patients. Blood 98: 23-28.
5. Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, et al. (2003) Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res 9: 606-612.
6. Bates GJ, Fox SB, Han C, Leek RD, Garcia JF, et al. (2006) Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol 24: 5373-5380.
7. Beyer M, Kochanek M, Darabi K, Popov A, Jensen M, et al. (2005) Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine. Blood 106: 2018-2025.
8. Tang Q, Bluestone JA, (2008) The Foxp3+ regulatory T cell: a jack of all trades, master of regulation. Nat Immunol 9: 239-244.
9. Knutson KL, Disis ML, Salazar LG, (2007) CD4 regulatory T cells in human cancer pathogenesis. Cancer Immunol Immunother 56: 271-285.
10. Curotto de Lafaille MA, Lafaille JJ, (2009) Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor? Immunity 30: 626-635.
11. Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T, Miyara M, et al. (2008) CTLA-4 control over Foxp3+ regulatory T cell function. Science 322: 271-275.
12. Huang CT, Workman CJ, Flies D, Pan X, Marson AL, et al. (2004) Role of LAG-3 in regulatory T cells. Immunity 21: 503-513.
13. Grossman WJ, Verbsky JW, Tollefsen BL, Kemper C, Atkinson JP, et al. (2004) Differential expression of granzymes A and B in human cytotoxic lymphocyte subsets and T regulatory cells. Blood 104: 2840-2848.
14. Strauss L, Bergmann C, Whiteside TL, (2009) Human circulating CD4+CD25highFoxp3+ regulatory T cells kill autologous CD8+ but not CD4+ responder cells by Fas-mediated apoptosis. J Immunol 182: 1469-1480.
15. Ito T, Hanabuchi S, Wang YH, Park WR, Arima K, et al. (2008) Two functional subsets of FOXP3+ regulatory T cells in human thymus and periphery. Immunity 28: 870-880.
16. Roncarolo MG, Gregori S, Battaglia M, Bacchetta R, Fleischhauer K, et al. (2006) Interleukin-10-secreting type 1 regulatory T cells in rodents and humans. Immunological reviews 212: 28-50.
17. Chen W, Jin W, Hardegen N, Lei KJ, Li L, et al. (2003) Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198: 1875-1886.
18. Garin MI, Chu CC, Golshayan D, Cernuda-Morollon E, Wait R, et al. (2007) Galectin-1: a key effector of regulation mediated by CD4+CD25+ T cells. Blood 109: 2058-2065.
19. Pandiyan P, Zheng L, Ishihara S, Reed J, Lenardo MJ, (2007) CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat Immunol 8: 1353-1362.
20. Sakaguchi S, Miyara M, Costantino CM, Hafler DA, (2010) FOXP3+ regulatory T cells in the human immune system. Nature reviews Immunology 10: 490-500.
21. Beyer M, Kochanek M, Giese T, Endl E, Weihrauch MR, et al. (2006) In vivo peripheral expansion of naive CD4+CD25high FoxP3+ regulatory T cells in patients with multiple myeloma. Blood 107: 3940-3949.
22. Brimnes MK, Vangsted AJ, Knudsen LM, Gimsing P, Gang AO, et al. (2010) Increased level of both CD4+FOXP3+ regulatory T cells and CD14+HLA-DR-/low myeloid-derived suppressor cells and decreased level of dendritic cells in patients with multiple myeloma. Scand J Immunol 72: 540-547.
23. Feyler S, von Lilienfeld-Toal M, Jarmin S, Marles L, Rawstron A, et al. (2009) CD4(+)CD25(+)FoxP3(+) regulatory T cells are increased whilst CD3(+)CD4(-)CD8(-) alphabetaTCR(+) Double Negative T cells are decreased in the peripheral blood of patients with multiple myeloma which correlates with disease burden. Br J Haematol 144: 686-695.
24. Pan X, Yuan X, Zheng Y, Wang W, Shan J, et al. (2012) Increased CD45RA+ FoxP3(low) regulatory T cells with impaired suppressive function in patients with systemic lupus erythematosus. PloS one 7: e34662.
25. Miyara M, Yoshioka Y, Kitoh A, Shima T, Wing K, et al. (2009) Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 30: 899-911.
26. Kruisbeek AM, Shevach E, Thornton AM (2004) Proliferative assays for T cell function. Current protocols in immunology/edited by John E Coligan [et al] Chapter 3: Unit 3 12.
27. Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, et al. (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10: 942-949.
28. Marshall NA, Christie LE, Munro LR, Culligan DJ, Johnston PW, et al. (2004) Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood 103: 1755-1762.
29. Farinha P, Al-Tourah A, Gill K, Klasa R, Connors JM, et al. (2010) The architectural pattern of FOXP3-positive T cells in follicular lymphoma is an independent predictor of survival and histologic transformation. Blood 115: 289-295.
30. Merlo A, Casalini P, Carcangiu ML, Malventano C, Triulzi T, et al. (2009) FOXP3 expression and overall survival in breast cancer. J Clin Oncol 27: 1746-1752.
31. Sasada T, Kimura M, Yoshida Y, Kanai M, Takabayashi A, (2003) CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression. Cancer 98: 1089-1099.
32. Giannopoulos K, Kaminska W, Hus I, Dmoszynska A (2012) The frequency of T regulatory cells modulates the survival of multiple myeloma patients: detailed characterisation of immune status in multiple myeloma. Br J Cancer.
33. Mizukami Y, Kono K, Kawaguchi Y, Akaike H, Kamimura K, et al. (2008) CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3+ regulatory T cells in gastric cancer. Int J Cancer 122: 2286-2293.
34. Hontsu S, Yoneyama H, Ueha S, Terashima Y, Kitabatake M, et al. (2004) Visualization of naturally occurring Foxp3+ regulatory T cells in normal and tumor-bearing mice. Int Immunopharmacol 4: 1785-1793.
35. Banerjee DK, Dhodapkar MV, Matayeva E, Steinman RM, Dhodapkar KM, (2006) Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after injection of cytokine-matured DCs in myeloma patients. Blood 108: 2655-2661.
36. Prabhala RH, Neri P, Bae JE, Tassone P, Shammas MA, et al. (2006) Dysfunctional T regulatory cells in multiple myeloma. Blood 107: 301-304.
37. Gupta R, Ganeshan P, Hakim M, Verma R, Sharma A, et al. (2011) Significantly reduced regulatory T cell population in patients with untreated multiple myeloma. Leuk Res 35: 874-878.
38. Atanackovic D, Cao Y, Luetkens T, Panse J, Faltz C, et al. (2008) CD4+CD25+FOXP3+ T regulatory cells reconstitute and accumulate in the bone marrow of patients with multiple myeloma following allogeneic stem cell transplantation. Haematologica 93: 423-430.
39. Beyer M, Schumak B, Weihrauch MR, Andres B, Giese T, et al. (2012) In vivo expansion of naive CD4+ CD25(high) FOXP3+ regulatory T cells in patients with colorectal carcinoma after IL-2 administration. PloS one 7: e30422.
40. Roodman GD, (1997) Mechanisms of bone lesions in multiple myeloma and lymphoma. Cancer 80: 1557-1563.
41. Sezer O, (2009) Myeloma bone disease: recent advances in biology, diagnosis, and treatment. Oncologist 14: 276-283.
42. Drayson M, Begum G, Basu S, Makkuni S, Dunn J, et al. (2006) Effects of paraprotein heavy and light chain types and free light chain load on survival in myeloma: an analysis of patients receiving conventional-dose chemotherapy in Medical Research Council UK multiple myeloma trials. Blood 108: 2013-2019.
43. Rossi F, Petrucci MT, Guffanti A, Marcheselli L, Rossi D, et al. (2009) Proposal and validation of prognostic scoring systems for IgG and IgA monoclonal gammopathies of undetermined significance. Clin Cancer Res 15: 4439-4445.
44. Giannopoulos K, Schmitt M, Kowal M, Wlasiuk P, Bojarska-Junak A, et al. (2008) Characterization of regulatory T cells in patients with B-cell chronic lymphocytic leukemia. Oncol Rep 20: 677-682.
45. Giannopoulos K, Schmitt M, Własiuk P, Chen J, Bojarska-Junak A, et al. (2008) The high frequency of T regulatory cells in patients with B-cell chronic lymphocytic leukemia is diminished through treatment with thalidomide. Leukemia 22: 222-224.
46. Ghiringhelli F, Larmonier N, Schmitt E, Parcellier A, Cathelin D, et al. (2004) CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur J Immunol 34: 336-344.
47. Takeuchi A, Eto M, Yamada H, Tatsugami K, Naito S, et al. (2011) A reduction of recipient regulatory T cells by cyclophosphamide contributes to an anti-tumor effect of nonmyeloablative allogeneic stem cell transplantation in mice. Int J Cancer.
48. Quach H, Ritchie D, Stewart AK, Neeson P, Harrison S, et al. (2010) Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma. Leukemia 24: 22-32.
49. Galustian C, Meyer B, Labarthe MC, Dredge K, Klaschka D, et al. (2009) The anti-cancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T regulatory cells. Cancer Immunol Immunother 58: 1033-1045.