Increased Frequency of CD8⁺ and CD4⁺ Regulatory T Cells in Chronic Lymphocytic Leukemia: Association with Disease Progression

REFERENCES

• Morton LM, Wang SS, Devesa SS, Hartge P, Weisenburger DD, Linet MS. Lymphoma incidence patterns by WHO subtype in the United States, 1992–2001. Blood 2006;107(1):265–276.
   Google Scholar
• Hojjat Farsangi M, Jeddi Tehrani M, Razavi SM, Sharifian RA, Mellstedt H, Shokri F, Rabbani H. Immunoglobulin heavy chain variable region gene usage and mutational status of the leukemic B cells in Iranian patients with chronic lymphocytic leukemia. Cancer Sci 2009;100(12):2346–2353.
   Google Scholar
• Matutes E, Owusu-Ankomah K, Morilla R, Garcia MJ, Houlihan A, Que T, Catvosky D. The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia 1994;8(10):1640–1645.
   Google Scholar
• Kay N, O'Brien S, Pettitt A, Stilgenbauer S. The role of prognostic factors in assessing “high-risk” subgroups of patients with chronic lymphocytic leukemia. Leukemia 2007;21(9):1885–1891.
   Google Scholar
• Orchard JA, Ibbotson RE, Davis Z, Wiestner A, Rosenwald A, Thomas PW, Hamblin TJ, Staudt LM, Oscier DG. ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet 2004;363(9403):105–111.
   Google Scholar
• Bouley J, Deriano L, Delic J, Merle-Béral H. New molecular markers in resistant B-CLL. Leukemia Lymphoma 2006;47(5): 791–801.
   Google Scholar
• Mougiakakos D, Choudhury A, Lladser A, Kiessling R, Johansson CC. Regulatory T cells in cancer. Adv Cancer Res 2010;107:57–117.
   Google Scholar
• Wilke CM, Wu K, Zhao E, Wang G, Zou W. Prognostic significance of regulatory T cells in tumor. Int J Cancer 2010;127(4):748–758.
   Google Scholar
• Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FoxP3+ regulatory T cells in the human immune system. Nat Rev Immunol 2010;10(7):490–500.
   Google Scholar
• Sakaguchi S. Naturally arising FoxP3-expressing CD25+ CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 2005;6(4):345–352.
   Google Scholar
• Smith TRF, Kumar V. Revival of CD8+ Treg-mediated suppression. Trends Immunol 2008;29(7):337–342.
   Google Scholar
• Filaci G, Fravega M, Negrini S, Procopio F, Fenoglio D, Rizzi M, Brenci S, Contini P, Olive D, Ghio M, Setti M, Accolla RS, Puppo F, Indiveri F. Nonantigen specific CD8+ T suppressor lymphocytes originate from CD8+ CD28– T cells and inhibit both T-cell proliferation and CTL function. Hum Immunol 2004;65(2):142–156.
   Google Scholar
• Joosten SA, Ottenhoff THM. Human CD4 and CD8 regulatory T cells in infectious diseases and vaccination. Hum Immunol 2008;69(11):760–770.
   Google Scholar
• Belkaid Y. Regulatory T cells and infection: a dangerous necessity. Nat Rev Immunol 2007;7(11):875–888.
   Google Scholar
• Beyer M, Kochanek M, Darabi K, Popov A, Jensen M, Endl E, Knolle PA, Thomas RK, von Bergwelt-Baildon M, Debey S, Hallek M, Schultze JL. Reduced frequencies and suppressive function of CD4+ CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine. Blood 2005;106(6):2018–2025.
   Google Scholar
• D'Arena G, Laurenti L, Minervini MM, Deaglio S, Bonello L, De Martino L, De Padua L, Savino L, Tarnani M, De Feo V, Cascavilla N. Regulatory T-cell number is increased in chronic lymphocytic leukemia patients and correlates with progressive disease. Leukemia Res 2011;35(3):363–368.
   Google Scholar
• Giannopoulos K, Schmitt M, Kowal M, Wlasiuk P, Bojarska-Junak A, Chen J, Rolinski J, Dmoszynska A. Characterization of regulatory T cells in patients with B-cell chronic lymphocytic leukemia. Oncol Rep 2008;20(3):677–682.
   Google Scholar
• Giannopoulos K, Schmitt M, lstrok P, Chen J, Bojarska-Junak A, Kowal M, Roliñski J, Dmoszyñska A. The high frequency of T regulatory cells in patients with B-cell chronic lymphocytic leukemia is diminished through treatment with thalidomide. Leukemia 2007;22(1):222–224.
   Google Scholar
• Jak M, Mous R, Remmerswaal EBM, Spijker R, Jaspers A, Yagüe A, Eldering E, Van Lier RA, Van Oers MH. Enhanced formation and survival of CD4+ CD25hi FoxP3+ T-cells in chronic lymphocytic leukemia. Leukemia Lymphoma 2009;50(5):788–801.
   Google Scholar
• Lindqvist CA, Christiansson LH, Thörn I, Mangsbo S, Paul Wetterberg G, Sundström C, Tötterman TH, Simonsson B, Enblad G, Frisk P, Olsson-Strömberg U, Loskog AS. Both CD4+ FoxP3+ and CD4+ FoxP3- T cells from patients with B cell malignancy express cytolytic markers and kill autologous leukaemic B cells in vitro. Immunol 2011;133(3):296–306.
   Google Scholar
• Weiss L, Melchardt T, Egle A, Grabmer C, Greil R, Tinhofer I. Regulatory T cells predict the time to initial treatment in early stage chronic lymphocytic leukemia. Cancer 2010;117(10):2163–2169.
   Google Scholar
• Kretz-Rommel A, Bowdish KS. Rationale for anti-CD200 immunotherapy in B-CLL and other hematologic malignancies: new concepts in blocking immune suppression. Expert Opin Biol Ther 2008;8(1):5–15.
   Google Scholar
• Pallasch CP, Ulbrich S, Brinker R, Hallek M, Uger RA, Wendtner C-M. Disruption of T cell suppression in chronic lymphocytic leukemia by CD200 blockade. Leukemia Res 2009;33(3): 460–464.
   Google Scholar
• Cheson BD, Bennett JM, Grever M, Kay N, Keating MJ, O'Brien S, Rai KR. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood 1996;87(12): 4990–4997.
   Google Scholar
• Molica S, De Rossi G, Luciani M, Levato D. Prognostic features and therapeutical approaches in B-cell chronic lymphocytic leukemia: an update. Haematologica 1995;80(2):176–193.
   Google Scholar
• Jaffe ES. The 2008 WHO classification of lymphomas: implications for clinical practice and translational research. Hematol 2009;2009(1):523–531.
   Google Scholar
• Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, Hillmen P, Keating MJ, Montserrat E, Rai KR, Kipps TJ; International Workshop on Chronic Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute—Working Group 1996 guidelines. Blood 2008;111(12):5446–5456.
   Google Scholar
• Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack B. Clinical staging of chronic lymphocytic leukemia. Blood 1975;46(2):219–234.
   Google Scholar
• Gharagozlou S, Gholam Alik, Rabbani H, Shokri F. Molecular analysis of the heavy chain variable region genes of human hybridoma clones specific for coagulation factor VIII. Thromb Haemostasis 2005;94(6):1131–1137.
   Google Scholar
• Dickinson A, George S, Proctor S. T cell subpopulations in CLL: methods of T cell enrichment artificially alter proportions of OKT4 and OKT8 positive cells. Clin Exp Immunol 1983;54(2):525–531.
   Google Scholar
• Kazemi T, Asgarian Omran H, Hojjat Farsangi M, Shabani M, Memarian A, Sharifian RA, Razavi SM, Jeddi-Tehrani M, Rabbani H, Shokri F. Fc receptor like 1-5 molecules are similarly expressed in progressive and indolent clinical subtypes of B cell chronic lymphocytic leukemia. Int J Cancer 2008;123(9):2113–2119.
   Google Scholar
• Younesi V, Nikzamir H, Yousefi M, Khoshnoodi J, Arjmand M, Rabbani H, Shokri F. Epstein Barr virus inhibits the stimulatory effect of TLR7/8 and TLR9 agonists but not CD40 ligand in human B lymphocytes. Microbiol Immunol 2010;54(9):534–541.
   Google Scholar
• Cosmi L, Liotta F, Lazzeri E, Francalanci M, Angeli R, Mazzinghi B, Santarlasci V, Manetti R, Vanini V, Romagnani P, Maggi E, Romagnani S, Annunziato F. Human CD8+ CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes. Blood 2003;102(12):4107–4114.
   Google Scholar
• Billerbeck E, Blum HE, Thimme R. Parallel expansion of human virus-specific FoxP3-effector memory and de novo-generated FoxP3+ regulatory CD8+ T cells upon antigen recognition in vitro. J. Immunol 2007;179(2):1039–1048.
   Google Scholar
• Joosten SA, Van Meijgaarden KE, Savage NDL, De Boer T, Triebel F, van Der Wal A, de Heer E, Klein MR, Geluk A, Ottenhoff TH. Identification of a human CD8+ regulatory T cell subset that mediates suppression through the chemokine CC chemokine ligand 4. Proc Natl Acad Sci USA 2007;104(19):8029–8034.
   Google Scholar
• Kim HJ, Verbinnen B, Tang X, Lu L, Cantor H. Inhibition of follicular T-helper cells by CD8+ regulatory T cells is essential for self tolerance. Nature 2010;467(7313):328–332.
   Google Scholar
• Colovai AI, Mirza M, Vlad G. Regulatory CD8+ CD28– T cells in heart transplant recipients. Hum Immunol 2003;64(1):31–37.
   Google Scholar
• Zhou H, Wang ZD, Zhu X, You Y, Zou P, (eds). CD8+ FoxP3+ T Cells From Renal Transplant Recipients in Quiescence Induce Immunoglobulin-Like Transcripts-3 and-4 on Dendritic Cells From Their Respective Donors. New York: Elsevier, 2007.
   Google Scholar
• Kreft KL, Verbraak E, Wierenga Wolf AF, Laman JD, Hintzen RQ. Role of CD8 regulatory T cells in multiple sclerosis. Ann Neurol 2010;69(3):593–594.
   Google Scholar
• Yang ZQ, Yang ZY, Zhang LD, Ping B, Wang SG, Ma KS, Li XW, Dong JH. Increased liver-infiltrating CD8+FoxP3+ regulatory T cells are associated with tumor stage in hepatocellular carcinoma patients. Hum Immunol 2010 Dec;71(12):1180–1186.
   Google Scholar
• Anichini A, Molla A, Vegetti C, Bersani I, Zappasodi R, Arienti F, Ravagnani F, Maurichi A, Patuzzo R, Santinami M, Pircher H, Di Nicola M, Mortarini R. Tumor-reactive CD8+ early effector T cells identified at tumor site in primary and metastatic melanoma. Cancer Res 2010;70(21):8378–8387.
   Google Scholar
• Chaput N, Louafi S, Bardier A, Charlotte F, Vaillant J, Ménégaux F, Rosenzwajg M, Lemoine F, Klatzmann D, Taieb J. Identification of CD8+ CD25+ FoxP3+ suppressive T cells in colorectal cancer tissue. Gut 2009;58(4):520–529.
   Google Scholar
• Kirk R. Risk factors: CD8+: FoxP3+ cell ratio is a novel survival marker for colorectal cancer. Nat Rev Clin Oncol 2010;7(6):299.
   Google Scholar
• Sobhani I, Le Gouvello S. Critical role for CD8+FoxP3+ regulatory T cells in colon cancer immune response in humans. Gut 2009;58(6):743–744.
   Google Scholar
• De Jong R, Leffers N, Boezen H, ten Hoor K, van der Zee A, Hollema H, Hollema H, Nijman HW. Presence of tumor-infiltrating lymphocytes is an independent prognostic factor in type I and II endometrial cancer. Gynecol Oncol 2009;114(1):105–110.
   Google Scholar
• Adurthi S, Krishna S, Mukherjee G, Bafna UD, Devi U, Jayshree RS. Regulatory T cells in a spectrum of HPV-induced cervical lesions: cervicitis, cervical intraepithelial neoplasia and squamous cell carcinoma. Am J Reprod Immunol 2008;60(1):55–65.
   Google Scholar
• Kiniwa Y, Miyahara Y, Wang HY, Peng W, Peng G, Wheeler TM, Thompson TC, Old LJ, Wang RF. CD8+ FoxP3+ regulatory T cells mediate immunosuppression in prostate cancer. Clin Cancer Res 2007;13(23):6947–6958.
   Google Scholar
• Janssens W, Carlier V, Wu B, VanderElst L, Jacquemin MG, Saint-Remy JMR. CD4+CD25+ T cells lyse antigen-presenting B cells by Fas-Fas ligand interaction in an epitope-specific manner. J. Immunol 2003;171(9):4604–4612.
   Google Scholar
• Zhao DM, Thornton AM, DiPaolo RJ, Shevach EM. Activated CD4+ CD25+ T cells selectively kill B lymphocytes. Blood 2006;107(10):3925–3932.
   Google Scholar
• Singh AK, Seavey CN, Horvath KA, Mohiuddin MM. Ex-vivo expanded baboon CD4+CD25Hi Treg cells suppress baboon anti-pig T and B cell immune response. Xenotransplantation 2012;19(2):102–111.
   Google Scholar
• Christopoulos P, Pfeifer D, Bartholomé K, Follo M, Timmer J, Fisch P, Veelken H. Definition and characterization of the systemic T-cell dysregulation in untreated indolent B-cell lymphoma and very early CLL. Blood 2011;117(14):3836–3846.
   Google Scholar
• Ravandi F, O'Brien S. Immune defects in patients with chronic lymphocytic leukemia. Cancer Immunol Immunother 2006;55(2):197–209.
   Google Scholar
• de Rezende LCD, Silva IV, Rangel LBA, Guimarães MCC. Regulatory T cell as a target for cancer therapy. Arch Immunol Ther Exp 2010;58(3):179–190.
   Google Scholar
• Elkord E, Alcantar-Orozco EM, Dovedi SJ, Tran DQ, Hawkins RE, Gilham DE. T regulatory cells in cancer: recent advances and therapeutic potential. Expert Opin Biol Ther 2010;10(11): 1573–1586.
   Google Scholar