Increased regulatory T cells in acute lymphoblastic leukaemia patients

Idris, Siti-Zuleha; Hassan, Norfarazieda; Lee, Le-Jie; Noor, Samsul Bahari Mohd; Osman, Raudhawati; Abdul-Jalil, Marsitah; Nordin, Abdul-Jalil; Abdullah, Maha

doi:10.1080/10245332.2015.1101965

Cited by 24 publications

(26 citation statements)

References 51 publications

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“…They play a central role in the maintenance of self‐tolerance and promote malignant cell progression by suppressing effective anti‐tumor immunity . In several different tumor entities, including hematological malignancies, a higher frequency of Treg was associated with an unfavorable clinical outcome . Hence, therapeutic options reducing Treg are encouraging treatment strategies for cancer control .…”

Section: Discussionmentioning

confidence: 99%

“…36 In several different tumor entities, including hematological malignancies, a higher frequency of Treg was associated with an unfavorable clinical outcome. [37][38][39][40][41] Hence, therapeutic options reducing Treg are encouraging treatment strategies for cancer control. 42,43 Antony et al 44 demonstrated that a CD8 + T cell immune response against antigens is hindered by Treg.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Donor lymphocyte infusion leads to diversity of specific T cell responses and reduces regulatory T cell frequency in clinical responders

Hofmann

Schmitt

Götz

et al. 2018

Intl Journal of Cancer

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T cell responses against malignant cells play a major role in maintaining remission and prolonging overall survival in patients after allogeneic stem cell transplantation and donor lymphocyte infusion (DLI) due to graft-versus-leukemia effect. For better characterization of the T cell responses, we assessed frequency and diversity of leukemia-associated antigen (LAA)-specific cytotoxic T cells using ELISpot and pMHC multimer assays and analyzed the frequency of regulatory T cells (Treg) as well as cytokine profiles before/after DLI. The data were correlated to the clinical course of patients. Significantly more LAA-derived T cell epitopes (p = 0.02) were recognized in clinical responders (R) when compared to nonresponders (NR). In addition, pMHC multimer-based flow cytometry showed a significantly higher frequency of LAA-specific T cells in R versus NR. The frequency of Treg in R decreased significantly (p = 0.008) while keeping stable in NR. No differences in T cell subset analysis before/after DLI were revealed. Clinical responders were correlated to specific immune responses and all clinical responders showed an increase of specific immune responses after DLI. Cytokine assays using enzyme-linked immunosorbent assay showed a significant increase of IL-4 after DLI. Taken together, an increase of specific CTL responses against several LAA after DLI was detected. Moreover, this study suggests that enhanced LAA diversity in T cell responses as well as decreasing numbers of Treg contribute to clinical outcome of patients treated with DLI.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Donor lymphocyte infusion leads to diversity of specific T cell responses and reduces regulatory T cell frequency in clinical responders

Hofmann

Schmitt

Götz

et al. 2018

Intl Journal of Cancer

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“…Tregs play a central role in the maintenance of self-tolerance and promote malignant cell progression by suppressing effective antitumor immunity [14], and thus it is truly striking that clinical responders in the analyzed patient cohort show a significant reduction of Treg. Further studies detected an association with a higher frequency of Treg and unfavorable clinical outcome in several other tumor entities including hematological malignancies [15][16][17][18][19].…”

Section: Understanding the Functionality Of Dli-immunological Effectsmentioning

confidence: 90%

Immunological and Clinical Impact of Manipulated and Unmanipulated DLI after Allogeneic Stem Cell Transplantation of AML Patients

Greiner

Götz

Bunjes

et al. 2019

JCM

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Allogeneic stem cell transplantation (allo-SCT) is the preferred curative treatment for several hematological malignancies. The efficacy of allo-SCT depends on the graft-versus-leukemia (GvL) effect. However, the prognosis of patients with relapsed acute myeloid leukemia (AML) following allo-SCT is poor. Donor lymphocyte infusion (DLI) is utilized after allo-SCT in this setting to prevent relapse, to prolong progression free survival, to establish full donor chimerism and to restore the GvL effect in patients with hematological malignancies. Thus, there are different options for the administration of DLI in AML patients. DLI is currently used prophylactically and in the setting of an overt relapse. In addition, in the minimal residual disease (MRD) setting, DLI may be a possibility to improve overall survival. However, DLI might increase the risk of severe life-threatening complications such as graft-versus-host disease (GvHD) as well as severe infections. The transfusion of lymphocytes has been tested not only for the treatment of hematological malignancies but also chronic infections. In this context, manipulated DLI in a prophylactic or therapeutic approach are an option, e.g., virus-specific DLI using different selection methods or antigen-specific DLI such as peptide-specific CD8+ cytotoxic T lymphocytes (CTLs). In addition, T cells are also genetically engineered, using both chimeric antigen receptor (CAR) genetically modified T cells and T cell receptor (TCR) genetically modified T cells. T cell therapies in general have the potential to enhance antitumor immunity, augment vaccine efficacy, and limit graft-versus-host disease after allo-SCT. The focus of this review is to discuss the different strategies to use donor lymphocytes after allo-SCT. Our objective is to give an insight into the functional effects of DLI on immunogenic antigen recognition for a better understanding of the mechanisms of DLI. To ultimately increase the GvL potency without raising the risk of GvHD at the same time.

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“…ACUTE lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children [1] . Patients with ALL receive intensive courses of chemotherapy which are followed by a period of leukopenia, Approximately three-quarters of patients express this common B-ALL precursor [2] .…”

Section: Introductionmentioning

confidence: 99%

miRNA Expression Profiling in Pediatric B-Cell Acute Lymphoblastic Leukemia by Microarray Technology

EL-SHARAWY¹,

Abdou²,

ZIDAN³

2018

The Medical Journal of Cairo University

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Background: MicroRNAs (miRNAs) are endogenous noncoding RNAs, which play an essential role in the regulation of gene expression. Aim of the work:To analyze miRNA expression profile in the childhood B acute lymphoblastic leukemia (B-ALL). To understand the functional regulatory effects of differential miRNAs on their targets and its clinical significance and novel analytical method to combine their expression profiles. Patients and Methods:In this study, we determined the relative expression analysis of miRNA and mRNA profiles in 20 childrenB-ALL patients. Through the use of miRNA microarray technology and according to their miRNA profile.The best characterized non-coding RNA family consists in humans of about 1400 microRNAs for which abundant evidence have demonstrated fundamental importance in normal development, differentiation, growth control and inhuman diseases such as cancer. : miR-100, miR-146a, miR-128a, miR-128b, miR-181a, miR-34, miR-193a, miR-193b, miR-151, miR-130b, and miR-125b were found to be the most consistently upregulated miRNAs in B-acute lymphoblastic leukemia patients as compared with healthy control. Results Conclusion:To analyze miRNA in B-ALL children patients before and after induction of chemotherapy and measure the correlation of these results using microarray technique.

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Increased regulatory T cells in acute lymphoblastic leukaemia patients

Cited by 24 publications

References 51 publications

Donor lymphocyte infusion leads to diversity of specific T cell responses and reduces regulatory T cell frequency in clinical responders

Donor lymphocyte infusion leads to diversity of specific T cell responses and reduces regulatory T cell frequency in clinical responders

Immunological and Clinical Impact of Manipulated and Unmanipulated DLI after Allogeneic Stem Cell Transplantation of AML Patients

miRNA Expression Profiling in Pediatric B-Cell Acute Lymphoblastic Leukemia by Microarray Technology

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