Peripheral Blood Lymphocyte Phenotype of Zap-70+ and Zap-70− Patients With B-Cell Chronic Lymphocytic Leukaemia

Abstract

Background: Up to now, the immune status of chronic lymphocytic leukemia (CLL) patients in association with the expression of zeta-chain-associated protein kinase 70 (ZAP-70) in leukemic cells has not been evaluated. Aim: The aim of this work was the study of the peripheral blood (PB) T-lymphocyte phenotypes in ZAP-70-positive (ZAP-70+) and ZAP-70-negative (ZAP-70−) untreated patients with CLL. Materials and Methods: ZAP-70-, CD25-, CD3-, CD4-, and CD8-positive lymphocytes were enumerated by flow cytometry in PB of 120 untreated CLL patients. CD8+, CD3+CD4+ and CD3+CD25+ cells were counted for the non-leukemic lymphocytes. Results: The patients were distributed into two groups: the ZAP-70+ group of high CLL progression (n = 61), and the ZAP-70− group of low CLL progression (n = 59). In the ZAP-70+ group, the ratio CD4/CD8 (0.33 ± 0.62; p = 0.001) and the numbers of the CD3+ (34.8 ± 8.1%; p = 0.01), CD3+CD4+ (24.4% ± 4.8; p = 0.001), and CD3+CD25+ (6.2 ± 0.91%; p = 0.001) lymphocytes were reduced and the percentage of the CD8+ cells (73.1 ± 4.6%; p = 0.0001) was above the norm. In the ZAP-70− group, the number of the CD3+CD4+ cells (36.9 ± 6.1%; p = 0.001) was within the norm, but the numbers of the CD8+ (11.3 ± 1.1%; p = 0.0001) and CD3+ (41.2 ± 5.3%; p = 0.05) lymphocytes were reduced; the ratio CD4/ CD8 (3.26 ± 0.88; p = 0.001) and the percentage of the CD3+CD25+ cells (27.1 ± 3.4%; p = 0.0001) were above the norm. Conclusions: Our data show that the increased CD4/CD8 ratio, caused by the reduced number of the CD8+ lymphocytes, and the increased number of CD3+CD25+ cells are characteristic for the ZAP-70− group (slow progressing) of untreated CLL patients. In ZAP-70+ patients, the CD4/CD8 ratio was significantly below the norm indicating an active disease process. Results of our study contribute to identification of CLL patients with different prognosis in routine diagnostic/prognostic procedures.

Relationship between the expression of CD25 and CD69 on the surface of lymphocytes T and B from peripheral blood and bone marrow of patients with chronic lymphocytic leukemia and established prognostic factors of this disease

“…The density of the expression of this molecule on leukemic cells is higher than on normal lymphocyte B, as well as on lymphocyte B during the so-called monoclonal B-cell lymphocytosis of undetermined significance (B-MLUS). [30][31][32][33][34] CD25 is postulated to be associated with the activation status of cells expressing this antigen.…”

Human CD3+ T-Cells with the Anti-ERBB2 Chimeric Antigen Receptor Exhibit Efficient Targeting and Induce Apoptosis in ERBB2 Overexpressing Breast Cancer Cells

“…Similar synergistic activity of CD4+ and CD8+ CAR-T cells has also been observed in murine models [ 44 ]. Moreover, PBMC consists of almost 70% CD3+ T-cells compared to only 21% of CD8+ T-cells [ 45 , 46 ]. Thus, adopting the strategy of transducing CAR into CD3+ T-cells could save both time and cost of cell preparation.…”

“…This study is significant in demonstrating that strategies employed to transduce CAR into human T-cells at CD3+ levels could give rise to effective ERBB2 antigen-specific CAR-T cell cytotoxic activity, and reduce the time and cost of CAR-T cell preparation [ 45 , 46 ]. CAR-T cells could overcome trastuzumab resistance and target tumours that express ERBB2 at moderate levels (e.g., osteosarcoma, glioblastoma, and medulloblastoma) that commonly escape trastuzumab treatment [ 60 ].…”

ZAP-70 Shapes the Immune Microenvironment in B Cell Malignancies

“…Mounting evidence indicates that the ZAP-70 expressed in tumor cells has ramifications for the composition of immune cells in the microenvironment, especially for the number of infiltrating T cells. In studies comparing the immune-phenotype of ZAP-70 positive and ZAP-70 negative CLL patients, tumor ZAP-70 expression was associated with increased CD4 central memory T cells and CD3/CD69+ T cells with decreased CD4/CD8 ratio in the peripheral blood (40)(41)(42). However, since high ZAP-70 expression is normally observed in only a subpopulation of CLL cells and varies substantially between patients, it is possible that subtle changes in different T cell populations between ZAP-70 positive and negative patients are partly impacted by inconsistencies in the definition of ZAP-70 positive in these studies.…”