scholarly journals Multidimensional scaling analysis identifies pathological and prognostically relevant profiles of circulating T-cells in chronic lymphocytic leukemia

2014 ◽  
Vol 135 (10) ◽  
pp. 2370-2379 ◽  
Author(s):  
Anne Rissiek ◽  
Christian Schulze ◽  
Ulrike Bacher ◽  
Aneta Schieferdecker ◽  
Benjamin Thiele ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Multidimensional Scaling ◽  
Lymphocytic Leukemia ◽  
Scaling Analysis ◽  
Multidimensional Scaling Analysis ◽  
Circulating T Cells

scholarly journals Multimarker analysis of T-cell chronic lymphocytic leukemia

Blood ◽  
1978 ◽  
Vol 51 (3) ◽  
pp. 435-438
Author(s):  
SM Marks ◽  
S Yanovich ◽  
DS Rosenthal ◽  
WC Moloney ◽  
SF Schlossman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Lymphoid Cells ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Cell Subpopulation ◽  
Skin Infiltration ◽  
Circulating T Cells

A 68-yr-old male with chronic lymphocytic leukemia (CLL) presented with splenomegaly and skin infiltration but no lymphadenopathy. The peripheral blood WBC cound was 300 x 10(9)/liter, with 95% small mature- appearing lymphocytes that were E-rosette positive and EAC-rosette negative. Further characterization of the patient's cells was performed using antisera with known lymphoid sub-population specificity. Anti- p23,30, which reacts with normal circulating B cells but not with T cells or thymocytes, was unreactive with the patient's cells. Anti-311, which reacts with both thymocytes and circulating T cells, was reactive with the patient's cells. Anti-Bk, which reacts only with thymocytes and not with circulating T-cells, failed to react with the patient's cells. The enzyme terminal deoxynucleotidyl transferase, present in thymocytes but absent for circulating T-cells, was also absent from the patient's lymphoid cells. Multimarker analysis therefore showed a mature T-lymphocyte phenotype on this patient's leukemia cells. Further functional analysis will probably show that such cells represent clonal expansion of a mature T-cell subpopulation, analogous to the B-cell clonality of common-variant CLL.

scholarly journals Lenalidomide induces long-lasting responses in elderly patients with chronic lymphocytic leukemia

Blood ◽  
2013 ◽  
Vol 122 (5) ◽  
pp. 734-737 ◽  
Author(s):  
Paolo Strati ◽  
Michael J. Keating ◽  
William G. Wierda ◽  
Xavier C. Badoux ◽  
Steliana Calin ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Elderly Patients ◽  
Lymphocytic Leukemia ◽  
Key Points ◽  
Circulating T Cells ◽  
Immunoglobulin Levels ◽  
Sustained Increase

Key Points Treatment with lenalidomide induces long-lasting responses. Lenalidomide can produce a sustained increase in immunoglobulin levels and a sustained normalization in circulating T cells.

scholarly journals Multimarker analysis of T-cell chronic lymphocytic leukemia

Blood ◽  
1978 ◽  
Vol 51 (3) ◽  
pp. 435-438 ◽  
Author(s):  
SM Marks ◽  
S Yanovich ◽  
DS Rosenthal ◽  
WC Moloney ◽  
SF Schlossman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Lymphoid Cells ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Cell Subpopulation ◽  
Skin Infiltration ◽  
Circulating T Cells

Abstract A 68-yr-old male with chronic lymphocytic leukemia (CLL) presented with splenomegaly and skin infiltration but no lymphadenopathy. The peripheral blood WBC cound was 300 x 10(9)/liter, with 95% small mature- appearing lymphocytes that were E-rosette positive and EAC-rosette negative. Further characterization of the patient's cells was performed using antisera with known lymphoid sub-population specificity. Anti- p23,30, which reacts with normal circulating B cells but not with T cells or thymocytes, was unreactive with the patient's cells. Anti-311, which reacts with both thymocytes and circulating T cells, was reactive with the patient's cells. Anti-Bk, which reacts only with thymocytes and not with circulating T-cells, failed to react with the patient's cells. The enzyme terminal deoxynucleotidyl transferase, present in thymocytes but absent for circulating T-cells, was also absent from the patient's lymphoid cells. Multimarker analysis therefore showed a mature T-lymphocyte phenotype on this patient's leukemia cells. Further functional analysis will probably show that such cells represent clonal expansion of a mature T-cell subpopulation, analogous to the B-cell clonality of common-variant CLL.

scholarly journals Targeting CD38 is lethal to Breg-like chronic lymphocytic leukemia cells and Tregs, but restores CD8+ T-cell responses

2020 ◽  
Vol 4 (10) ◽  
pp. 2143-2157 ◽  
Author(s):  
Alak Manna ◽  
Timothy Kellett ◽  
Sonikpreet Aulakh ◽  
Laura J. Lewis-Tuffin ◽  
Navnita Dutta ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Xenograft Model ◽  
Lymphocytic Leukemia ◽  
Dependent Manner

Abstract Patients with chronic lymphocytic leukemia (CLL) are characterized by monoclonal expansion of CD5+CD23+CD27+CD19+κ/λ+ B lymphocytes and are clinically noted to have profound immune suppression. In these patients, it has been recently shown that a subset of B cells possesses regulatory functions and secretes high levels of interleukin 10 (IL-10). Our investigation identified that CLL cells with a CD19+CD24+CD38hi immunophenotype (B regulatory cell [Breg]–like CLL cells) produce high amounts of IL-10 and transforming growth factor β (TGF-β) and are capable of transforming naive T helper cells into CD4+CD25+FoxP3+ T regulatory cells (Tregs) in an IL-10/TGF-β-dependent manner. A strong correlation between the percentage of CD38+ CLL cells and Tregs was observed. CD38hi Tregs comprised more than 50% of Tregs in peripheral blood mononuclear cells (PBMCs) in patients with CLL. Anti-CD38 targeting agents resulted in lethality of both Breg-like CLL and Treg cells via apoptosis. Ex vivo, use of anti-CD38 monoclonal antibody (mAb) therapy was associated with a reduction in IL-10 and CLL patient-derived Tregs, but an increase in interferon-γ and proliferation of cytotoxic CD8+ T cells with an activated phenotype, which showed an improved ability to lyse patient-autologous CLL cells. Finally, effects of anti-CD38 mAb therapy were validated in a CLL–patient-derived xenograft model in vivo, which showed decreased percentage of Bregs, Tregs, and PD1+CD38hiCD8+ T cells, but increased Th17 and CD8+ T cells (vs vehicle). Altogether, our results demonstrate that targeting CD38 in CLL can modulate the tumor microenvironment; skewing T-cell populations from an immunosuppressive to immune-reactive milieu, thus promoting immune reconstitution for enhanced anti-CLL response.

Regulatory T cells in chronic lymphocytic leukemia: implication for immunotherapeutic interventions

Tumor Biology ◽  
2013 ◽  
Vol 34 (4) ◽  
pp. 2031-2039 ◽  
Author(s):  
Farhad Jadidi-Niaragh ◽  
Ghasem Ghalamfarsa ◽  
Mehdi Yousefi ◽  
Mina Hajifaraj Tabrizi ◽  
Fazel Shokri
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Regulatory T Cells ◽  
Lymphocytic Leukemia

scholarly journals Immunological and genetic kinetics from diagnosis to clinical progression in chronic lymphocytic leukemia

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Isabel Jiménez ◽  
Bárbara Tazón-Vega ◽  
Pau Abrisqueta ◽  
Juan C. Nieto ◽  
Sabela Bobillo ◽  
...  
Keyword(s):  
T Cells ◽  
Chronic Lymphocytic Leukemia ◽  
Ex Vivo ◽  
Clonal Evolution ◽  
Lymphocytic Leukemia ◽  
Clinical Progression ◽  
Molecular Changes ◽  
Main Driver ◽  
Altered Gene

Abstract Background Mechanisms driving the progression of chronic lymphocytic leukemia (CLL) from its early stages are not fully understood. The acquisition of molecular changes at the time of progression has been observed in a small fraction of patients, suggesting that CLL progression is not mainly driven by dynamic clonal evolution. In order to shed light on mechanisms that lead to CLL progression, we investigated longitudinal changes in both the genetic and immunological scenarios. Methods We performed genetic and immunological longitudinal analysis using paired primary samples from untreated CLL patients that underwent clinical progression (sampling at diagnosis and progression) and from patients with stable disease (sampling at diagnosis and at long-term asymptomatic follow-up). Results Molecular analysis showed limited and non-recurrent molecular changes at progression, indicating that clonal evolution is not the main driver of clinical progression. Our analysis of the immune kinetics found an increasingly dysfunctional CD8+ T cell compartment in progressing patients that was not observed in those patients that remained asymptomatic. Specifically, terminally exhausted effector CD8+ T cells (T-betdim/−EomeshiPD1hi) accumulated, while the the co-expression of inhibitory receptors (PD1, CD244 and CD160) increased, along with an altered gene expression profile in T cells only in those patients that progressed. In addition, malignant cells from patients at clinical progression showed enhanced capacity to induce exhaustion-related markers in CD8+ T cells ex vivo mainly through a mechanism dependent on soluble factors including IL-10. Conclusions Altogether, we demonstrate that the interaction with the immune microenvironment plays a key role in clinical progression in CLL, thereby providing a rationale for the use of early immunotherapeutic intervention.

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