CD4+CD25highCD127low/-FoxP3+ Regulatory T Cell Subpopulations in the Bone Marrow and Peripheral Blood of Children
M Niedźwiecki1, O Budziło1, M Zieliński2
1Department of Pediatrics, Hematology and Oncology, Medical University of Gdansk, Gdańsk, Poland.
Insights
Regulatory T cells (Tregs) are elevated in the bone marrow of children with acute lymphoblastic leukemia (ALL). These Tregs, particularly memory Tregs, correlate with disease progression and therapeutic response, suggesting their role in ALL pathogenesis.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- Regulatory T cells (Tregs) are crucial for immune homeostasis.
- Tregs are implicated in autoimmune diseases and cancer progression, including leukemia.
- The specific role of Treg dysregulation in Chronic Lymphocytic Leukemia (CLL) and Acute Lymphoblastic Leukemia (ALL) remains debated.
Purpose of the Study:
- To investigate the role and distribution of regulatory T cells (Tregs) in pediatric acute lymphoblastic leukemia (ALL).
- To analyze the correlation between Treg levels and clinical parameters in ALL patients.
- To explore the potential of Tregs as prognostic indicators and therapeutic targets in ALL.
Main Methods:
- Analysis of CD4+CD25highCD127low/-FoxP3+ Tregs in bone marrow and peripheral blood of 42 children with ALL.
- Subpopulation analysis of Tregs, focusing on memory Tregs.
- Correlation analysis between Treg percentages and clinical markers (blasts, Hb, minimal residual disease, leukocytosis) before and during therapy.
Main Results:
- A statistically higher percentage of Tregs was observed in the bone marrow compared to peripheral blood in pediatric ALL patients.
- Memory Tregs interacting with leukemic antigens showed significant differences.
- Negative correlations were found between bone marrow Tregs and blast percentage, minimal residual disease, and leukocytosis.
- A positive correlation was noted between bone marrow Tregs and Hb levels before therapy.
Conclusions:
- Treg cell distribution and levels differ between bone marrow and peripheral blood in pediatric ALL.
- Tregs, particularly memory Tregs, appear to influence the clinical course and therapeutic outcomes in ALL.
- Tregs may serve as potential prognostic markers and targets for immunotherapy in ALL.
Abstract:
CD4+CD25highCD127low/-FoxP3+ regulatory T cells (Tregs) are currently under extensive investigation in childhood acute lymphoblastic leukemia (ALL) and in other human cancers. Usually, Treg cells maintain the immune cell homeostasis. This small subset of T cells has been, in fact, considered to be involved in the pathogenesis of autoimmune diseases and progression of acute and chronic leukemias. However, whether Treg dysregulation in CLL and ALL plays a key role or it rather represents a simple epiphenomenon is still a matter of debate. Treg cells have been proposed as a prognostic indicator of the clinical course of the disease and might also be used for targeted immune therapy. Our study revealed statistically higher percentage of Treg cells in the bone marrow than in peripheral blood in the group of 42 children with acute lymphoblastic leukemia. By analyzing Treg subpopulations, it was shown that only memory Tregs in contact with leukemic antigens showed statistically significant differences. We noticed a low negative correlation between Treg cells in the bone marrow and the percentage of blasts (R = -0.36) as well as a moderate correlation between Treg cells in the bone marrow and Hb level (R = +0.41) in peripheral blood before therapy. The number of peripheral blood blasts on day 8th correlates negatively (R = -0.36) with Tregs. Furthermore, statistical analysis revealed low negative correlation between the number of Tregs in the bone marrow and the minimal residual disease measured on day 15th, the percentage of blasts in the bone marrow and leukocytosis after 15 days of chemotherapy. These results indicate the influence of Tregs on the final therapeutic effect.
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