Table of Contents Author Guidelines Submit a Manuscript
Journal of Immunology Research
Volume 2017, Article ID 1832968, 13 pages
https://doi.org/10.1155/2017/1832968
Review Article

Regulatory T Cells and Their Prognostic Relevance in Hematologic Malignancies

1Hematology and Stem Cell Transplantation Unit, IRCCS Cancer Referral Center of Basilicata, Rionero in Vulture, Italy
2Division of Hematology, AOU Città della Salute e della Scienza di Torino, University of Torino, Torino, Italy
3Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy
4Dipartimento di Biochimica, Biofisica e Patologia Generale, University of Campania “Luigi Vanvitelli”, Napoli, Italy
5Department of Clinical Medicine and Surgery, Regional Reference Centre for Coagulation Disorders, “Federico II” University, Napoli, Italy
6Department of Pharmacology, University of Salerno, Salerno, Italy
7Department of Biomedical and Dental Sciences and Morphological and Functional Sciences, University of Messina, Messina, Italy
8Hematology Institute, Catholic University of Sacred Heart, Rome, Italy
9Scientific Direction, IRCCS Cancer Referral Center of Basilicata, Rionero in Vulture, Italy
10Centre of Excellence for Biomedical Research, Department of Internal Medicine, IRCCS Azienda Ospedaliero Universitaria San Martino-IST-Istituto Nazionale per la Ricerca sul Cancro, University of Genoa, Genoa, Italy

Correspondence should be addressed to Giovanni D’Arena; ti.orebil@aneradinnavoig

Received 17 August 2017; Accepted 14 November 2017; Published 21 December 2017

Academic Editor: Wenxin Zheng

Copyright © 2017 Giovanni D’Arena et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. Sakaguchi, K. Wing, and M. Miyara, “Regulatory T cells – a brief history and perspective,” European Journal of Immunology, vol. 37, Supplement 1, pp. S116–S123, 2007. View at Publisher · View at Google Scholar · View at Scopus
  2. R. K. Gershon and K. Kondo, “Cell interactions in the induction of tolerance: the role of thymic lymphocytes,” Immunology, vol. 18, no. 5, pp. 723–737, 1970. View at Google Scholar
  3. S. Sakaguchi, N. Sakaguchi, M. Asano, M. Itoh, and M. Toda, “Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chain (CD25). breakdown of a single mechanism of self-tolerance causes various autoimmune disease,” Journal of Immunology, vol. 155, pp. 1151–1164, 1995. View at Google Scholar
  4. C. Baecher-Allan, J. A. Brown, G. J. Freeman, and D. A. Hafler, “CD4+CD25high regulatory cells in human peripheral blood,” Journal of Immunology, vol. 167, no. 3, pp. 1245–1253, 2001. View at Publisher · View at Google Scholar
  5. R. J. Robb, A. Munck, and K. A. Smith, “T cell growth factor receptors. Quantitation, specificity, and biological relevance,” Journal of Experimental Medicine, vol. 154, no. 5, pp. 1455–1474, 1981. View at Publisher · View at Google Scholar
  6. S. Hori, T. Numura, and S. Sakaguchi, “Control of regulatory T cell development by the transcription factor FoxP3,” Science, vol. 299, no. 5609, pp. 1057–1061, 2003. View at Publisher · View at Google Scholar · View at Scopus
  7. J. D. Fontenot, M. A. Gavin, and A. Y. Rudensky, “FoxP3 programs the development and function of CD4+CD25+ regulatory T cells,” Nature Immunology, vol. 4, no. 4, pp. 330–336, 2003. View at Publisher · View at Google Scholar · View at Scopus
  8. C. L. Bennett, J. Christie, F. Ramsdell et al., “The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3,” Nature Genetics, vol. 27, no. 1, pp. 20-21, 2001. View at Publisher · View at Google Scholar · View at Scopus
  9. N. Seddiki, B. Santner-Nanan, J. Martinson et al., “Expression of interleukin (IL)-2 and IL-7 receptors discriminate between human regulatory and activated T cells,” Journal of Experimental Medicine, vol. 203, no. 7, pp. 1693–1700, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. W. Liu, A. L. Putnam, Z. Xu-Yu et al., “CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ Treg cells,” Journal of Experimental Medicine, vol. 203, pp. 1701–1711, 2006. View at Publisher · View at Google Scholar · View at Scopus
  11. M. Beyer and J. L. Schultze, “Regulatory T cells in cancer,” Blood, vol. 108, no. 3, pp. 804–811, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. T. L. Whiteside, “The role of regulatory T cells in cancer immunology,” ImmunoTargets and Therapy, vol. 4, pp. 159–171, 2015. View at Publisher · View at Google Scholar
  13. Y. Takeuchi and H. Nishikawa, “Roles of regulatory T cells in cancer immunity,” International Immunology, vol. 28, no. 8, pp. 401–409, 2016. View at Publisher · View at Google Scholar · View at Scopus
  14. J. Wang and X. Y. Ke, “The Four types of Tregs in malignant lymphomas,” Journal Hematological & Oncology, vol. 4, p. 50, 2011. View at Publisher · View at Google Scholar · View at Scopus
  15. P. Farinha, A. Al-Tourah, K. Gill, R. Klasa, J. M. Connors, and R. D. Gascoyne, “The architectural pattern of FOXP3-positive T cells in follicular lymphoma is an independent predictor of survival and histologic transformation,” Blood, vol. 115, no. 2, pp. 289–295, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. R. Droeser, I. Zlobec, E. Kilic et al., “Differential pattern and prognostic significance of CD4+, FOXP3+ and IL-7+ tumor infiltrating lymphocytes in ductal and lobular breast cancers,” BMC Cancer, vol. 12, no. 1, p. 134, 2012. View at Publisher · View at Google Scholar · View at Scopus
  17. N. Chiorazzi, K. R. Rai, and M. Ferrarini, “Chronic lymphocytic leukemia,” New England Journal of Medicine, vol. 352, no. 8, pp. 804–815, 2005. View at Publisher · View at Google Scholar · View at Scopus
  18. F. Forconi and P. Moss, “Perturbation of the normal immune system in patients with CLL,” Blood, vol. 126, no. 5, pp. 573–581, 2015. View at Publisher · View at Google Scholar · View at Scopus
  19. M. E. Wallace, M. B. Alcantara, M. Yosuke, G. Kannourakis, and S. P. Berzins, “An emerging role for immune regulatory subsets in chronic lymphocytic leukaemia,” International Immunopharmacology, vol. 28, no. 2, pp. 897–900, 2015. View at Publisher · View at Google Scholar · View at Scopus
  20. G. D’Arena, V. Simeon, F. D’Auria et al., “Regulatory T-cells in chronic lymphocytic leukemia: actor or innocent bystander?” American Journal of Blood Research, vol. 3, no. 1, pp. 52–57, 2013. View at Google Scholar
  21. G. D'Arena, G. Rossi, B. Vannata et al., “Regulatory T-cells in chronic lymphocytic leukemia and autoimmune diseases,” Mediterranean Journal of Hematology and Infectious Diseases, vol. 4, no. 1, article e2012053, 2012. View at Publisher · View at Google Scholar · View at Scopus
  22. M. Jak, R. Mous, E. B. Remmerswaal et al., “Enhanced formation and survival of CD4+ CD25hi FoxP3+ T-cells in chronic lymphocytic leukemia,” Leukemia & Lymphoma, vol. 50, no. 5, pp. 788–801, 2009. View at Publisher · View at Google Scholar · View at Scopus
  23. G. D’Arena, L. Laurenti, M. M. Minervini et al., “Regulatory T-cell number is increased in chronic lymphocytic leukemia patients and correlates with progressive disease,” Leukemia Research, vol. 35, no. 3, pp. 363–368, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. G. D’Arena, F. D’Auria, V. Simeon et al., “A shorter time to the first treatment may be predicted by the absolute number of regulatory T-cells in patients with Rai stage 0 chronic lymphocytic leukemia,” American Journal of Hematology, vol. 87, no. 6, pp. 628–631, 2012. View at Publisher · View at Google Scholar · View at Scopus
  25. L. Weiss, T. Melchardt, A. Egle, C. Grabmer, R. Greil, and I. Tinhofer, “Regulatory T cells predict the time to initial treatment in early stage chronic lymphocytic leukemia,” Cancer, vol. 117, no. 10, pp. 2163–2169, 2011. View at Publisher · View at Google Scholar · View at Scopus
  26. D. P. Lad, S. Varma, N. Varma, M. U. Sachdeva, P. Bose, and P. Malhotra, “Regulatory T-cells in B-cell chronic lymphocytic leukemia: their role in disease progression and autoimmune cytopenias,” Leukemia and Lymphoma, vol. 54, pp. 1012–1019, 2013. View at Publisher · View at Google Scholar · View at Scopus
  27. A. Biancotto, P. K. Dagur, J. C. Fuchs, A. Wiestner, C. B. Bagwell, and J. P. McCoy Jr., “Phenotypic complexity of T regulatory subsets in patients with B-chronic lymphocytic leukemia,” Modern Pathology, vol. 25, no. 2, pp. 246–259, 2012. View at Publisher · View at Google Scholar · View at Scopus
  28. A. Dasgupta, M. Mahapatra, and R. Saxena, “A study for proposal of use of regulatory T cells as a prognostic marker and establishing an optimal threshold level for their expression in chronic lymphocytic leukemia,” Leukemia & Lymphoma, vol. 56, no. 6, pp. 1831–1838, 2015. View at Publisher · View at Google Scholar · View at Scopus
  29. V. E. Mpakou, H. D. Ioannidou, E. Konsta et al., “Quantitative and qualitative analysis of regulatory T cells in B cell chronic lymphocytic leukemia,” Leukemia Research, vol. 60, pp. 74–81, 2017. View at Publisher · View at Google Scholar
  30. G. D’Arena, G. Rossi, M. M. Minervini et al., “Circulating regulatory T cells in “clinical” monoclonal B-cell lymphocytosis,” International Journal of Immunopathology and Pharmacology, vol. 24, no. 4, pp. 915–923, 2011. View at Publisher · View at Google Scholar
  31. A. Rissiek, C. Schulze, U. Bacher et al., “Multidimensional scaling analysis identifies pathological and prognostically relevant profiles of circulating T-cells in chronic lymphocytic leukemia,” International Journal Cancer, vol. 135, pp. 2370–2379, 2014. View at Publisher · View at Google Scholar · View at Scopus
  32. D. Rossi, E. C. Sozzi, A. Puma et al., “The prognosis of clinical monoclonal B cell lymphocytosis differs from prognosis of Rai 0 chronic lymphocytic leukemia and is recapitulated by biological risk factors,” British Journal of Haematology, vol. 146, no. 1, pp. 64–75, 2009. View at Publisher · View at Google Scholar · View at Scopus
  33. G. D’Arena and P. Musto, “Monoclonal B-cell lymphocytosis,” Translational Medicine, vol. 8, pp. 75–79, 2014. View at Google Scholar
  34. M. Beyer, M. Kochanek, K. Darabi et al., “Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine,” Blood, vol. 106, no. 6, pp. 2018–2025, 2005. View at Publisher · View at Google Scholar · View at Scopus
  35. K. P. Piper, M. Karanth, A. McLarnon et al., “Chronic lymphocytic leukaemia cells drive the global CD4+ T cell repertoire towards a regulatory phenotype and leads to the accumulation of CD4+ forkhead box P3+ T cells,” Clinical & Experimental Immunology, vol. 166, no. 2, pp. 154–163, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Coscia, C. Vitale, S. Peola et al., “Dysfunctional Vγ9Vδ2 T cells are negative prognosticators and markers of dysregulated mevalonate pathway activity in chronic lymphocytic leukemia cells,” Blood, vol. 120, no. 16, pp. 3271–3279, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. B. N. Lee, H. Gao, E. N. Cohen et al., “Treatment with lenalidomide modulates T-cell immunophenotype and cytokine production in patients with chronic lymphocytic leukemia,” Cancer, vol. 117, no. 17, pp. 3999–4008, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. G. D’Arena, V. Simeon, L. De Martino et al., “T-cell modulation by green tea in chronic lymphocytic leukemia,” International Journal Immunopathology Pharmacology, vol. 26, pp. 117–125, 2013. View at Publisher · View at Google Scholar
  39. G. D’Arena, L. Laurenti, M. Coscia et al., “Complementary and alternative medicine use in patients with chronic lymphocytic leukemia: an Italian multicentric survey,” Leukemia & Lymphoma, vol. 55, no. 4, pp. 841–847, 2014. View at Publisher · View at Google Scholar · View at Scopus
  40. Z.-Z. Yang, A. J. Novak, S. C. Ziesmer, T. E. Witzig, and S. M. Ansell, “Attenuation of CD8+ T-cell function by CD4+CD25+ regulatory T cells in B-cell non-Hodgkin’s lymphoma,” Cancer Research, vol. 66, no. 20, pp. 10145–10152, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. N. A. Marshall, L. E. Christei, L. R. Murro et al., “Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma,” Blood, vol. 103, no. 5, pp. 1755–1762, 2004. View at Publisher · View at Google Scholar · View at Scopus
  42. S. Schreck, D. Friebel, M. Buettner et al., “Prognostic impact of tumour-infiltrating Th2 and regulatory T cells in classical Hodgkin lymphoma,” Hematological Oncology, vol. 27, no. 1, pp. 31–39, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. A. Tzankov, C. Meier, P. Hirschmann, P. Went, S. A. Pileri, and S. Dirnhofer, “Correlation of high numbers of intratumoral FOXP3+ regulatory T cells with improved survival in germinal center-like diffuse large B-cell lymphoma, follicular lymphoma and classical Hodgkin’s lymphoma,” Haematologica, vol. 93, no. 2, pp. 193–200, 2008. View at Publisher · View at Google Scholar · View at Scopus
  44. T. Alvaro, M. Lejeune, M. T. Salvado et al., “Outcome in Hodgkin’s lymphoma can be predicted from the presence of accompanying cytotoxic and regulatory T cells,” Clinical Cancer Research, vol. 11, no. 4, pp. 1467–1473, 2005. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Garcia, B. Bellosillo, B. Sánchez-González et al., “Study of regulatory T-cells in patients with gastric Malt lymphoma: influence on treatment response and outcome,” PLoS One, vol. 7, no. 12, article e51681, 2012. View at Publisher · View at Google Scholar · View at Scopus
  46. C. Chang, S. Y. Wu, Y. W. Kang et al., “High levels of regulatory T cells in blood are a poor prognostic factor in patients with diffuse large B-cell lymphoma,” American Journal Clinical Pathology, vol. 144, pp. 935–944, 2015. View at Publisher · View at Google Scholar · View at Scopus
  47. A. F. Koreishi, A. J. Saenz, D. O. Persky et al., “The role of cytotoxic and regulatory T-cells in relapsed/refractory Hodgkin lymphoma,” Apllied Immunohistochemistry & molecular Morphology, vol. 18, pp. 206–211, 2010. View at Publisher · View at Google Scholar · View at Scopus
  48. W. Y. Kim, Y. K. Jeon, T. M. Kim et al., “Increased quantity of tumor-infiltrating FOXP3-positive regulatory T cells is an independent predictor for improved clinical outcome in extranodal NK/T-cell lymphoma,” Annals Oncology, vol. 20, pp. 1688–1696, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. J. Carreras, A. Lopez-Guillermo, B. C. Fox et al., “High numbers of tumor-infiltrating FOXP3-positive regulatory T-cells are associated with improved overall survival in follicular lymphoma,” Blood, vol. 108, no. 9, pp. 2957–2964, 2006. View at Publisher · View at Google Scholar · View at Scopus
  50. R. H. Prabhala, P. Neri, J. E. Bae et al., “Dysfunctional T regulatory cells in multiple myeloma,” Blood, vol. 107, no. 1, pp. 301–304, 2006. View at Publisher · View at Google Scholar · View at Scopus
  51. G. D’Arena, G. Rossi, L. Laurenti et al., “Circulating regulatory T-cells in monoclonal gammopathies of uncertain significance and multiple myeloma: in search of a role,” Journal of Immunology Research, vol. 2016, Article ID 9271469, 7 pages, 2016. View at Publisher · View at Google Scholar · View at Scopus
  52. M. Beyer, M. Kochanek, T. Giese et al., “In vivo peripheral expansion of naive CD4+ CD25high FoxP3+ regulatory T cells in patients with multiple myeloma,” Blood, vol. 107, no. 10, pp. 3940–3949, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. S. Feyler, M. von Lilenfeld-Toal, S. Jarmin et al., “CD4+ CD25+ FoxP3+ regulatory T cells are increased whilst CD3+ CD4 CD8 αβTCR+ double negative T cells are decreased in the peripheral blood of patients with multiple myeloma which correlates with disease burden,” British Journal of Haematology, vol. 144, no. 5, pp. 686–695, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. R. Gupta, P. Ganeshan, M. Hakim, R. Verma, A. Sharma, and L. Kumar, “Significantly reduced regulatory T cell population in patients with untreated multiple myeloma,” Leukemia Research, vol. 35, no. 7, pp. 874–878, 2011. View at Publisher · View at Google Scholar · View at Scopus
  55. K. R. Muthu Raja, L. Rihova, L. Zahradova, M. Klincova, M. Penka, and R. Hajek, “Increased T regulatory cells are associated with adverse clinical features and predict progression in multiple myeloma,” PLoS One, vol. 7, no. 10, article e47077, 2012. View at Publisher · View at Google Scholar · View at Scopus
  56. K. Giannopoulos, W. Kaminska, I. Hus, and A. Dmoszynska, “The frequency of T regulatory cells modulates the survival of multiple myeloma patients: detailed characterization of immune status in multiple myeloma,” British Journal of Cancer, vol. 106, no. 3, pp. 546–552, 2012. View at Publisher · View at Google Scholar · View at Scopus
  57. M. Foglietta, B. Castella, S. Mariani et al., “The bone marrow of myeloma patients is steadily inhibited by a normal-sized pool of functional regulatory T cells irrespective of the disease status,” Haematologica, vol. 99, no. 10, pp. 1605–1610, 2014. View at Publisher · View at Google Scholar · View at Scopus
  58. K. Bhattacharya, S. Chandra, and C. Mandal, “Critical stoichiometric ratio of CD4+ CD25+ FoxP3+ regulatory T cells and CD4+ CD25 responder T cells influence immunosuppression in patients with B-cell acute lymphoblastic leukaemia,” Immunology, vol. 142, pp. 124–139, 2013. View at Publisher · View at Google Scholar · View at Scopus
  59. C.-P. Wu, X. Quing, H. Zhu, and H.-Y. Zhou, “Immunophenotype and increased presence of CD4+CD25+ regulatory T cells in patients with acute lymphoblastic leukemia,” Oncology Letters, vol. 3, no. 2, pp. 421–424, 2012. View at Publisher · View at Google Scholar · View at Scopus
  60. X. Wang, J. Zheng, J. Liu et al., “Increased population of CD4+CD25high regulatory T cells with their higher apoptotic and proliferating status in peripheral blood of acute myeloid leukemia patients,” European Journal of Haematology, vol. 75, no. 6, pp. 468–476, 2005. View at Publisher · View at Google Scholar · View at Scopus
  61. S. Z. Idris, N. Hassan, L. J. Lee et al., “Increased regulatory T cells in acute lymphoblastic leukemia patients,” Hematology, vol. 20, no. 9, pp. 523–529, 2015. View at Publisher · View at Google Scholar · View at Scopus
  62. A. M. Zahran, H. Badrawy, and A. Ibrahim, “Prognostic value of regulatory T cells in newly diagnosed chronic myeloid leukemia patients,” International Journal of Clinical Oncology, vol. 19, no. 4, pp. 753–760, 2014. View at Publisher · View at Google Scholar · View at Scopus
  63. J. M. Rojas, L. Wang, S. Owen, K. Knight, S. J. Watmough, and R. E. Clark, “Naturally occurring CD4+ CD25+ FOXP3+T-regulatory cells are increased in chronic myeloid leukemia patients not in complete cytogenetic remission and can be immunosuppressive,” Experimental Hematology, vol. 38, no. 12, pp. 1209–1218, 2010. View at Publisher · View at Google Scholar · View at Scopus
  64. E. Nadal, M. Garin, J. Kaeda, J. Apperley, R. Lechlir, and F. Dazzi, “Increased frequencies of CD4+CD25high Tregs correlate with disease relapse after allogeneic stem cell transplantation for chronic myeloid leukemia,” Leukemia, vol. 21, no. 3, pp. 472–479, 2007. View at Publisher · View at Google Scholar · View at Scopus
  65. I. Hus, J. Tabarkiewicz, M. Lewandowska et al., “Evaluation of monocyte-derived dendritic cells, T regulatory and Th17 cells in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors,” Folia Histochemistry Cytobiologica, vol. 49, no. 1, pp. 153–160, 2011. View at Publisher · View at Google Scholar · View at Scopus
  66. C. R. Hasselbalch, M. K. Jensen, K. M. Brimnes et al., “Increase in circulating CD4+CD25+Foxp3+ T cells in patients with Philadelphia-negative chronic myeloproliferative neoplasms during treatment with IFN-α,” Blood, vol. 118, pp. 2170–2173, 2011. View at Publisher · View at Google Scholar · View at Scopus
  67. M. Kovacsovics-Bankowski, T. W. Kelley, O. Efimova et al., “Changes in peripheral blood lymphocytes in polycythemia vera and essential thrombocythemia patients treated with pegylated-interferon alpha and correlation with JAK2V617F allelic burden,” Experimental Hematology & Oncology, vol. 5, p. 28, 2016. View at Publisher · View at Google Scholar · View at Scopus
  68. M. Massa, R. Campanelli, G. Fois et al., “Reduced frequency of circulating CD4+CD25brightCD127lowFOXP3+ regulatory T cells in primary myelofibrosis,” Blood, vol. 128, no. 12, pp. 1660–1662, 2016. View at Publisher · View at Google Scholar
  69. M. Massa, V. Rosti, R. Campanelli, G. Fois, and G. Barosi, “Rapid and long-lasting decrease of T-regulatory cells in patients with myelofibrosis treated with ruxolitinib,” Leukemia, vol. 28, no. 2, pp. 449–451, 2014. View at Publisher · View at Google Scholar · View at Scopus
  70. J. C. Wang, H. Sindhu, C. Chen et al., “Immune derangements in patients with myelofibrosis: the role of Treg, Th17, and sIL2Rα,” PLoS One, vol. 10, no. 3, article e0116723, 2015. View at Publisher · View at Google Scholar · View at Scopus
  71. S. P. Yajnanarayana, T. Stubig, I. Cornez et al., “JAK1/2 inhibition impairs T cell function in vitro and in patients with myeloproliferative neoplasms,” British Journal of Haematology, vol. 169, no. 6, pp. 824–833, 2015. View at Publisher · View at Google Scholar · View at Scopus
  72. K. Wang and A. T. Vella, “Regulatory T cells and cancer: a two-sided story,” Immunology Investigation, vol. 45, no. 8, pp. 797–812, 2016. View at Publisher · View at Google Scholar · View at Scopus
  73. K. Giannopoulos, M. Schmitt, M. Kowal et al., “Characterization of regulatory T cells in patients with B-cell chronic lymphocytic leukemia,” Oncology Report, vol. 20, pp. 677–682, 2008. View at Publisher · View at Google Scholar · View at Scopus
  74. E. Bachy, J. Bernaud, P. Roy, D. Rigal, and F. E. Nicolini, “Quantitative and functional analyses of CD4+CD25+FoxP3+ regulatory T cells in chronic phase chronic myeloid leukaemia patients at diagnosis and on imatinib mesylate,” British Journal of Haematology, vol. 153, pp. 129–143, 2011. View at Publisher · View at Google Scholar · View at Scopus