The Mysterious Actor—γδ T Lymphocytes in Chronic Lymphocytic Leukaemia (CLL)

Zarobkiewicz, Michał K.; Bojarska‐Junak, Agnieszka

doi:10.3390/cells11040661

Cited by 5 publications

(7 citation statements)

References 119 publications

(182 reference statements)

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“…Gamma-delta T cells are severely affected by the CLL disease burden. 13 However, current data suggest that this applies unequally to different subsets. While Vδ2 cells show signs of exhaustion and are usually almost unresponsive, Vδ1 cells remain highly active in a large portion of CLL patients.…”

Section: Introductionmentioning

confidence: 62%

“…Therefore, the majority of γδ T cell research is oriented towards the Vδ2 subtype. 12,13 Vδ1 cells constitute the 2 nd largest portion of γδ T cells in peripheral blood, but due to more complicated protocols for their expansion, they are far less understood. 14 Vδ3, Vδ4 and Vδ5 are virtually unstudied, mostly due to the lack of appropriate monoclonal antibodies that enable easy immunophenotyping or sorting.…”

Section: Introductionmentioning

confidence: 99%

“…9,15 Indeed, expansion and domination of Vδ1 may have an important positive influence on the course of CLL. 13,15 While the clinical-grade large-scale expansion of autologous Vδ2 lymphocytes currently seems unreachable, there are such attempts with Vδ1 cells. 14 Nevertheless, successful immunotherapy with Vδ1 cells requires a better understanding of the impact that CLL has on both γδ T cells as a whole and their non-Vδ2 compartment.…”

Section: Introductionmentioning

confidence: 99%

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Expression of CD226 on γδ T cells is lower in advanced chronic lymphocytic leukemia and correlates with IgA, IgG and LDH levels

Zarobkiewicz,

Lehman,

Kowalska

et al. 2024

Adv Clin Exp Med

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Background. Gamma-delta (γδ) T cells comprise an important subset of human T cells, responding to viral and bacterial infections, and are significant for cancer immunosurveillance. Human γδ T cells are divided into 5 major subsets, namely Vδ1-Vδ5, of which the latter 3 have limited available literature. At present, Vδ2 is the most studied subpopulation.Objectives. In the current paper, we focused on non-Vδ2 cells in chronic lymphocytic leukemia (CLL). We assessed the expression of co-inhibitory checkpoint receptors (CTLA-4, PD-1 and TIGIT) and co-stimulatory (CD226 and NKp30) molecules separately on Vδ1 and Vδ3-Vδ5 cells. Materials and methods.We assessed γδ T cells for their expression of both cytotoxicity-related (NKp30, CD226) and co-inhibitory (PD-1, TIGIT) molecules with flow cytometry in CLL patients. Moreover, we evaluated the expression of TIGIT and CD226 ligand (PVR , CD155) in neoplastic B cells in CLL patients with quantitative real-time polymerase chain reaction (qPCR).Results. A significant accumulation of Vδ1 T cells was noted, while no difference was observed in the total percentage of Vδ2 cells. Contrary to our initial hypothesis, the impact of CLL burden on CD226 and TIGIT expression was lower than anticipated. The former tends to be lower in more advanced disease. Finally, a strong upregulation of CD155 (PVR) was noted on CLL-derived B cells when compared to healthy B cells.Conclusions. Chronic lymphocytic leukemia regulates the expression of the CD155-CD226/TIGIT axis. Contrary to expectations, the ligand is significantly more affected than the receptors. Nevertheless, the relatively high expression of CD155 and TIGIT makes CLL an interesting target for anti-TIGIT immunotherapy.

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Section: Introductionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression of CD226 on γδ T cells is lower in advanced chronic lymphocytic leukemia and correlates with IgA, IgG and LDH levels

Zarobkiewicz,

Lehman,

Kowalska

et al. 2024

Adv Clin Exp Med

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“…Furthermore, miR∼17-92, but especially miR-20a, is capable of significant silencing of MIC-A/B and ULBPs, important ligands for NKG2D [ 31 ]. This may significantly lower the cytotoxic response of γδ T and NK cells as both populations widely express NKG2D [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of the miR-17~92 Cluster in Chronic Lymphocytic Leukemia

Chocholska

Zarobkiewicz

Szymańska

et al. 2023

IJMS

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The aim of this study was to investigate the expression of miR-17∼92 cluster members in chronic lymphocytic leukemia (CLL) patients. Six microRNAs (miRNAs)—miR-17, miR-18a, miR-19a, miR-19b-1, miR-20a, and miR-92a-1—very poorly characterized in CLL patients, were chosen for the study to consider their possible role as cancer biomarkers. It is currently unclear to which extent miR-17~92 expression is related to other routinely measured CLL markers, and whether the findings can be of any clinical significance. To achieve this goal, we report the expression levels of these miRNAs detected by RT-qPCR in purified CD19+ B lymphocytes of 107 CLL patients and correlate them with existing clinical data. The study provides new evidence regarding the heterogeneity of miR-17~92 cluster members’ expression in CLL patients. Higher miR-17-5p expression was associated with unfavorable prognostic factors (i.e., 17p and 11q deletions, CD38 and ZAP-70 expression). On the other hand, miR-19a, miR-20a, and miR-92a-1 negatively correlated with these adverse factors. The presence of del(13q) as a sole aberration was associated with a significantly lower miR-17-5p as well as higher miR-19a-3p and miR-92a-1-5p expression compared to patients carrying unfavorable genetic aberrations. Particularly, miR-20a could be considered an independent favorable prognostic factor. In a multivariate analysis, high miR-20a expression remained an independent marker predicting long TTT (time to treatment) for CLL patients.

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“…The cells that constitute the microenvironment are possibly recruited actively by CLL cells. In turn, microenvironmental cells interact through cell-to-cell contacts and produce soluble factors that promote the survival of CLL cells, as well as contribute to BCR activation [8].…”

Section: Introductionmentioning

confidence: 99%

Active Hexose-Correlated Compound Shows Direct and Indirect Effects against Chronic Lymphocytic Leukemia

Merchand-Reyes,

Santhanam,

Valencia-Pena

et al. 2023

Nutrients

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Chronic lymphocytic leukemia (CLL) is a disease characterized by the accumulation of mature CD19+CD5+CD23+ B cells in the bloodstream and in lymphoid organs. It usually affects people over 70 years of age, which limits the options for treatments. The disease is typically well-managed, but to date is still incurable. Hence, the need for novel therapeutic strategies remains. Nurse-like cells (NLCs) are major components of the microenvironment for CLL, supporting tumor cell survival, proliferation, and even drug resistance. They are of myeloid lineage, guided toward differentiating into their tumor-supportive role by the CLL cells themselves. As such, they are analogous to tumor-associated macrophages and represent a major therapeutic target. Previously, it was found that a mushroom extract, Active Hexose-Correlated Compound (AHCC), promoted the death of acute myeloid leukemia cells while preserving normal monocytes. Given these findings, it was asked whether AHCC might have a similar effect on the abnormally differentiated myeloid-lineage NLCs in CLL. CLL-patient PBMCs were treated with AHCC, and it was found that AHCC treatment showed a direct toxic effect against isolated CLL cells. In addition, it significantly reduced the number of tumor-supportive NLCs and altered their phenotype. The effects of AHCC were then tested in the Eµ-TCL1 mouse model of CLL and the MllPTD/WT Flt3ITD/WT model of AML. Results showed that AHCC not only reduced tumor load and increased survival in the CLL and AML models, but it also enhanced antitumor antibody treatment in the CLL model. These results suggest that AHCC has direct and indirect effects against CLL and that it may be of benefit when combined with existing treatments.

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The Mysterious Actor—γδ T Lymphocytes in Chronic Lymphocytic Leukaemia (CLL)

Cited by 5 publications

References 119 publications

Expression of CD226 on γδ T cells is lower in advanced chronic lymphocytic leukemia and correlates with IgA, IgG and LDH levels

Expression of CD226 on γδ T cells is lower in advanced chronic lymphocytic leukemia and correlates with IgA, IgG and LDH levels

Prognostic Value of the miR-17~92 Cluster in Chronic Lymphocytic Leukemia

Active Hexose-Correlated Compound Shows Direct and Indirect Effects against Chronic Lymphocytic Leukemia

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