Clinical Significance of Treg Cell Frequency in Acute Myeloid Leukemia

Overview

Journal Int J Hematol

Specialty Hematology

Date 2013 Oct 22

PMID 24142765

Citations 21

Authors

Wenjuan Yang

Yunxiao Xu

Affiliations

Soon will be listed here.

Abstract

This study was designed to investigate the clinical significance of peripheral blood CD4(+) CD25(+) CD127 low-regulatory T (T(reg)) cells in acute myeloid leukemia (AML) patients. T(reg) cells in the peripheral blood of 80 AML patients and 35 age-matched healthy controls were counted by flow cytometry. Correlations between the frequency of circulating T(reg) cells and disease status, treatment outcome, or prognosis were evaluated. The percentages of T(reg) cells in patients at diagnosis and during refractory/relapse were significantly higher than that in healthy controls. There was no significant difference in the percentages of T(reg) cells between patients in remission and healthy controls. After six cycles of chemotherapy, the percentage of T(reg) cells in patients who achieved complete remission was significantly lower than that in patients at diagnosis, but there was no difference in T(reg) frequency between refractory/relapse patients and patients at diagnosis. T(reg) cells in the peripheral blood of AML patients may play a suppressive role in host antitumor immune response. The frequency of T(reg) cells in peripheral blood may thus be used as a biomarker for predicting sensitivity to chemotherapy and prognosis of AML patients. Additionally, T(reg) number in peripheral blood could be used to monitor disease status and evaluate disease progression.

Citing Articles

Divergent CD4 T-cell profiles are associated with anti-HLA alloimmunization status in platelet-transfused AML patients.

Khelfa M, Leclerc M, Kerbrat S, Boudjemai Y, Benchouaia M, Neyrinck-Leglantier D Front Immunol. 2023; 14:1165973.

PMID: 37701444 PMC: 10493329. DOI: 10.3389/fimmu.2023.1165973.

NK cell defects: implication in acute myeloid leukemia.

DSilva S, Singh M, Pinto A Front Immunol. 2023; 14:1112059.

PMID: 37228595 PMC: 10203541. DOI: 10.3389/fimmu.2023.1112059.

Dendritic Cell-Triggered Immune Activation Goes along with Provision of (Leukemia-Specific) Integrin Beta 7-Expressing Immune Cells and Improved Antileukemic Processes.

Rackl E, Li L, Klauer L, Ugur S, Pepeldjiyska E, Seidel C Int J Mol Sci. 2023; 24(1).

PMID: 36613907 PMC: 9820538. DOI: 10.3390/ijms24010463.

High expression of B4GALT1 is associated with poor prognosis in acute myeloid leukemia.

Ren Z, Huang X, Lv Q, Lei Y, Shi H, Wang F Front Genet. 2022; 13:882004.

PMID: 36568388 PMC: 9780537. DOI: 10.3389/fgene.2022.882004.

Targeting the Tumor Microenvironment in Acute Myeloid Leukemia: The Future of Immunotherapy and Natural Products.

Hino C, Pham B, Park D, Yang C, Nguyen M, Kaur S Biomedicines. 2022; 10(6).

PMID: 35740430 PMC: 9219790. DOI: 10.3390/biomedicines10061410.

References

Pandolfi F, Cianci R, Lolli S, Dunn I, Newton E, Haggerty T . Strategies to overcome obstacles to successful immunotherapy of melanoma. Int J Immunopathol Pharmacol. 2008; 21(3):493-500. PMC: 2915778. DOI: 10.1177/039463200802100302. View

Grauer O, Sutmuller R, van Maren W, Jacobs J, Bennink E, Toonen L . Elimination of regulatory T cells is essential for an effective vaccination with tumor lysate-pulsed dendritic cells in a murine glioma model. Int J Cancer. 2007; 122(8):1794-802. DOI: 10.1002/ijc.23284. View

Clark R, Huang S, Murphy G, Mollet I, Hijnen D, Muthukuru M . Human squamous cell carcinomas evade the immune response by down-regulation of vascular E-selectin and recruitment of regulatory T cells. J Exp Med. 2008; 205(10):2221-34. PMC: 2556796. DOI: 10.1084/jem.20071190. View

Mato A, Morgans A, Luger S . Novel strategies for relapsed and refractory acute myeloid leukemia. Curr Opin Hematol. 2008; 15(2):108-14. DOI: 10.1097/MOH.0b013e3282f463d2. View

Ersvaer E, Liseth K, Skavland J, Gjertsen B, Bruserud O . Intensive chemotherapy for acute myeloid leukemia differentially affects circulating TC1, TH1, TH17 and TREG cells. BMC Immunol. 2010; 11:38. PMC: 2912832. DOI: 10.1186/1471-2172-11-38. View

Chu Y, Wang L, Yang G, Ross H, Urba W, Prell R . Efficacy of GM-CSF-producing tumor vaccine after docetaxel chemotherapy in mice bearing established Lewis lung carcinoma. J Immunother. 2006; 29(4):367-80. DOI: 10.1097/01.cji.0000199198.43587.ba. View

Kanakry C, Hess A, Gocke C, Thoburn C, Kos F, Meyer C . Early lymphocyte recovery after intensive timed sequential chemotherapy for acute myelogenous leukemia: peripheral oligoclonal expansion of regulatory T cells. Blood. 2010; 117(2):608-17. PMC: 3031483. DOI: 10.1182/blood-2010-04-277939. View

Griffiths R, Elkord E, Gilham D, Ramani V, Clarke N, Stern P . Frequency of regulatory T cells in renal cell carcinoma patients and investigation of correlation with survival. Cancer Immunol Immunother. 2007; 56(11):1743-53. PMC: 11030591. DOI: 10.1007/s00262-007-0318-z. View

Curiel T, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P . Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004; 10(9):942-9. DOI: 10.1038/nm1093. View

10.

Fu J, Xu D, Liu Z, Shi M, Zhao P, Fu B . Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology. 2007; 132(7):2328-39. DOI: 10.1053/j.gastro.2007.03.102. View

11.

Robak T, Wrzesien-Kus A . The search for optimal treatment in relapsed and refractory acute myeloid leukemia. Leuk Lymphoma. 2002; 43(2):281-91. DOI: 10.1080/10428190290006053. View

12.

Ustun C, Miller J, Munn D, Weisdorf D, Blazar B . Regulatory T cells in acute myelogenous leukemia: is it time for immunomodulation?. Blood. 2011; 118(19):5084-95. PMC: 3217399. DOI: 10.1182/blood-2011-07-365817. View

13.

Smits E, Berneman Z, Van Tendeloo V . Immunotherapy of acute myeloid leukemia: current approaches. Oncologist. 2009; 14(3):240-52. DOI: 10.1634/theoncologist.2008-0165. View

14.

Kelley T, Parker C . CD4 (+)CD25 (+)Foxp3 (+) regulatory T cells and hematologic malignancies. Front Biosci (Schol Ed). 2010; 2(3):980-92. DOI: 10.2741/s114. View

15.

Curti A, Pandolfi S, Valzasina B, Aluigi M, Isidori A, Ferri E . Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25- into CD25+ T regulatory cells. Blood. 2006; 109(7):2871-7. DOI: 10.1182/blood-2006-07-036863. View

16.

Beyer M, Schultze J . Regulatory T cells in cancer. Blood. 2006; 108(3):804-11. DOI: 10.1182/blood-2006-02-002774. View

17.

Shenghui Z, Yixiang H, Jianbo W, Kang Y, Laixi B, Yan Z . Elevated frequencies of CD4⁺ CD25⁺ CD127lo regulatory T cells is associated to poor prognosis in patients with acute myeloid leukemia. Int J Cancer. 2010; 129(6):1373-81. DOI: 10.1002/ijc.25791. View

18.

Szczepanski M, Szajnik M, Czystowska M, Mandapathil M, Strauss L, Welsh A . Increased frequency and suppression by regulatory T cells in patients with acute myelogenous leukemia. Clin Cancer Res. 2009; 15(10):3325-32. PMC: 3700356. DOI: 10.1158/1078-0432.CCR-08-3010. View

19.

Wang X, Zheng J, Liu J, Yao J, He Y, Li X . Increased population of CD4(+)CD25(high), regulatory T cells with their higher apoptotic and proliferating status in peripheral blood of acute myeloid leukemia patients. Eur J Haematol. 2005; 75(6):468-76. DOI: 10.1111/j.1600-0609.2005.00537.x. View

20.

Ghiringhelli F, Menard C, Puig P, Ladoire S, Roux S, Martin F . Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother. 2006; 56(5):641-8. PMC: 11030569. DOI: 10.1007/s00262-006-0225-8. View