Abstract
Introduction: Leukemia cells are able to escape from immunosurveillance using immune tolerance mechanisms as the majority of leukemia antigens are either shared or aberrantly expressed self-proteins. T cells reactive to these antigens are purged during thymic selection. CD2, a pan-T-cell antigen, is expressed early during T cell developments in thymus and is found on all subsets of mature T cells. Recent studies show that there are low levels of extrathymic CD2 negative (CD2-) T cells, which show immature T cell features and can be induced to differentiate into mature helper and cytotoxic T cells in vitro. Since circulating CD2- T cells could represent pre-selection immature T cells, they may play an important role in tumor immunity.
Methods: 81 pediatric B-cell acute lymphoblastic leukemia (B-ALL) patients, 22 pediatric acute myeloid leukemia (AML) patients and 22 normal controls were included in this study. B-ALL group included 45 NCI-standard risk (SR) patients and 36 NCI-high risk patients. All the leukemia patients were diagnosed at Children's Mercy Hospital in the past ten years with a diagnostic peripheral blood (PB) specimen. The PB specimens were studied by four-color multiparameter flow cytometry with antibodies for T cell markers (CD2, CD3, CD4, CD5, CD7 and CD8) and CD45, and analyzed by BD FACSDiva 8.0.1. CD2- and CD3+ T cells were recorded as % of total T cells. Student's t-test was used to compare results.
Results: The percentages of CD2- T cells in AML (mean ± STD: 1.31% ± 1.41%) and B-ALL (0.84% ± 0.67%) were significantly higher than that seen in control group (0.51% ± 0.52%, p<0.05). No significant difference was found between AML and B-ALL. There was no significant difference between HR B-ALL (0.96% ± 0.81%) and SR B-ALL (0.74% ± 0.52%). Interestingly, CD2- T cells in 4/5 B-ALLs with 11q23 (KMT2A) rearrangement were undetectable. All 3 therapy-related AML patients studied had KMT2A gene rearrangement, and had no detectable CD2- T cells with poor clinical outcome (overall survival less than 1 year). The 3 AMLs associated with Down syndrome, a prognostically favorable AML group, showed relative high levels (≥ 1.49%) of CD2- T cells.
Conclusions: Circulating CD2- T cells are increased in peripheral blood in pediatric AML and B-ALL patients. KMT2A gene rearrangement, an unfavorable cytogenetic abnormality, is associated with a decrease in CD2- T cells. The relationship of KMT2A gene rearrangement and decrease in circulating CD2- T-cells as well as the relationship of CD2- T cells to clinical outcome should be evaluated in future studies. The role of CD2- T cells in tumor specific immunomodulation should be explored, and may impact future studies of cell-based cancer immunotherapeutics.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
