Chemotherapy alters the increased numbers of myeloid-derived suppressor and regulatory T cells in children with acute lymphoblastic leukemia

被引:36
作者
Salem, Mohamed Labib [1 ,2 ]
El-Shanshory, Mohamed R. [1 ,3 ]
Abdou, Said H. [1 ,4 ]
Attia, Mohamed S. [1 ,4 ]
Sobhy, Shymaa M. [1 ,2 ]
Zidan, Mona F. [1 ,2 ]
Zidan, Abdel-Aziz A. [1 ,5 ]
机构
[1] Tanta Univ, CECR, Tanta, Egypt
[2] Tanta Univ, Fac Sci, Dept Zool, Tanta, Egypt
[3] Tanta Univ, Fac Med, Pediat Oncol, Tanta, Egypt
[4] Tanta Univ, Fac Med, Clin Pathol, Tanta, Egypt
[5] Damanhour Univ, Dept Zool, Damanhour, Egypt
关键词
Acute lymphoblastic leukemia; immunosuppressive cells; myeloid-derived suppressor cells; regulatory T cells; PERIPHERAL-BLOOD; CANCER-PATIENTS; DIFFERENTIATION; IMMUNOSUPPRESSION; MICROENVIRONMENT; IDENTIFICATION; IMMUNOTHERAPY; MECHANISM; EXPANSION; STAGE;
D O I
10.1080/08923973.2018.1424897
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Introduction: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children. The precise mechanism behind the relapse in this disease is not clearly known. One possible mechanism could be the accumulation of immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs) and T regulatory cells (T-regs) which we and others have reported to mediate suppression of anti-tumor immune responses. Aim: In this study, we aimed to analyze the numbers of these cells in a population of B-ALL pediatric patients. Methods: Peripheral blood samples withdrawn from B-ALL pediatric patients (n = 45 before, during and after the induction phase of chemotherapy. Using multi parametric flow cytometric analysis. MDSCs were identified as Lin(-)HLA-DR(-)CD33(+)CD11b(+); and T-reg cells were defined as CD4(+)CD25(+)CD127(-/low). Results: Early diagnosed B-ALL patients showed significant increases in the numbers of MDSCs and T-regs as compared to healthy volunteers. During induction of chemotherapy, however, the patients showed higher and lower numbers of MDSCs and T-reg cells, respectively as compared to early diagnosed patients (i.e., before chemotherapy). After induction of chemotherapy, the numbers of MDSCs and T-reg cells showed higher increases and decreases, respectively as compared to the numbers in patients during chemotherapy. Conclusion: Our results indicate that B-ALL patients harbor high numbers of both MDSCs and T-regs cells. This pilot study opens a new avenue to investigate the mechanism mediating the emergence of these cells on larger number of B-ALL patients at different treatment stages.
引用
收藏
页码:158 / 167
页数:10
相关论文
共 55 条
[1]  
Abe Y, 2000, Rinsho Ketsueki, V41, P1277
[2]  
Almand B, 2000, CLIN CANCER RES, V6, P1755
[3]   Increased production of immature myeloid cells in cancer patients: A mechanism of immunosuppression in cancer [J].
Almand, B ;
Clark, JI ;
Nikitina, E ;
van Beynen, J ;
English, NR ;
Knight, SC ;
Carbone, DP ;
Gabrilovich, DI .
JOURNAL OF IMMUNOLOGY, 2001, 166 (01) :678-689
[4]   The Dark Side of Cyclophosphamide: Cyclophosphamide-Mediated Ablation of Regulatory T Cells [J].
Becker, Juergen C. ;
Schrama, David .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2013, 133 (06) :1462-1465
[5]   In vivo peripheral expansion of naive CD4+CD25high FoxP3+ regulatory T cells in patients with multiple myeloma [J].
Beyer, Marc ;
Kochanek, Matthias ;
Giese, Thomas ;
Endl, Elmar ;
Weihrauch, Martin R. ;
Knolle, Percy A. ;
Classen, Sabine ;
Schultze, Joachim L. .
BLOOD, 2006, 107 (10) :3940-3949
[6]   Comparative Approach to Define Increased Regulatory T Cells in Different Cancer Subtypes by Combined Assessment of CD127 and FOXP3 [J].
Beyer, Marc ;
Classen, Sabine ;
Endl, Elmar ;
Kochanek, Matthias ;
Weihrauch, Martin R. ;
Debey-Pascher, Svenja ;
Knolle, Percy A. ;
Schultze, Joachim L. .
CLINICAL & DEVELOPMENTAL IMMUNOLOGY, 2011,
[7]   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 [J].
Bhattacharya, Kaushik ;
Chandra, Sarmila ;
Mandal, Chitra .
IMMUNOLOGY, 2014, 142 (01) :124-139
[8]   Myeloid-derived suppressor cells in multiple myeloma: pre-clinical research and translational opportunities [J].
Botta, Cirino ;
Gulla, Annemaria ;
Correale, Pierpaolo ;
Tagliaferri, Pierosandro ;
Tanssone, Pierfrancesco .
FRONTIERS IN ONCOLOGY, 2014, 4
[9]   Identification of a CD11b+/Gr-1+/CD31+ myeloid progenitor capable of activating or suppressing CD8+ T cells [J].
Bronte, V ;
Apolloni, E ;
Cabrelle, A ;
Ronca, R ;
Serafini, P ;
Zamboni, P ;
Restifo, NP ;
Zanovello, P .
BLOOD, 2000, 96 (12) :3838-3846
[10]   Regulatory T-cell inhibition versus depletion: the right choice in cancer immunotherapy [J].
Colombo, Mario P. ;
Piconese, Silvia .
NATURE REVIEWS CANCER, 2007, 7 (11) :880-887