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T Cells In Chronic ...
T Cells In Chronic Lymphocytic Leukemia Display Dysregulated Expression Of Immune Checkpoints And Activation Markers
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Palma, Marzia (författare)
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Gentilcore, Giusy (författare)
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Heimersson, Kia (författare)
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Mozaffari, Fariba (författare)
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Näsman-Glaser, Barbro (författare)
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Young, Emma (författare)
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Rosenquist, Richard (författare)
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Hansson, Lotta (författare)
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Österborg, Anders (författare)
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Mellstedt, Håkan (författare)
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- 2017
- 2017
- Engelska.
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Ingår i: Haematologica. - 0390-6078. ; 102:3, 562-572
Abstract
Ämnesord
Stäng
- Chronic lymphocytic leukemia is characterized by impaired immune functions largely due to profound T-cell defects. T-cell functions also depend on co-signaling receptors, inhibitory or stimulatory, known as immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1). Here we analyzed the T-cell phenotype focusing on immune checkpoints and activation markers in chronic lymphocytic leukemia patients (n=80) with different clinical characteristics and compared them to healthy controls. In general, patients had higher absolute numbers of CD3+ cells and the CD8+ subset was particularly expanded in previously treated patients. Progressive patients had higher numbers of CD4+ and CD8+ cells expressing PD-1 compared to healthy controls, which was more pronounced in previously treated patients (P=0.0003 and P=0.001, respectively). A significant increase in antigen-experienced T cells was observed in patients within both the CD4+ and CD8+ subsets, with a significantly higher PD-1 expression. Higher numbers of CD4+ and CD8+ cells with intracellular CTLA-4 were observed in patients, as well as high numbers of proliferating (Ki67+) and activated (CD69+) CD4+ and CD8+ cells, more pronounced in patients with active disease. The numbers of Th1, Th2, Th17 and regulatory T cells were substantially increased in patients compared to controls (P<0.05), albeit decreasing to low levels in pre-treated patients. In conclusion, chronic lymphocytic leukemia T cells display increased expression of immune checkpoints, abnormal subset distribution, and a higher proportion of proliferating cells compared to healthy T cells. Disease activity and previous treatment shape the T-cell profile of chronic lymphocytic leukemia patients in different ways.
Ämnesord
- Medical and Health Sciences (hsv)
- Clinical Medicine (hsv)
- Hematology (hsv)
- Medicin och hälsovetenskap (hsv)
- Klinisk medicin (hsv)
- Hematologi (hsv)
- Molekylär medicin (uu)
- Molecular Medicine (uu)
Nyckelord
- SURFACE EXPRESSION; PERIPHERAL-BLOOD; CD152 CTLA-4; CLL PATIENTS; B-CLL; EXPANSION; SUBSETS; STAGE; PD-1; LENALIDOMIDE
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Till lärosätets databas
- Av författaren/redakt...
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Palma, Marzia
-
Gentilcore, Gius ...
-
Heimersson, Kia
-
Mozaffari, Farib ...
-
Näsman-Glaser, B ...
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Young, Emma
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visa fler...
-
Rosenquist, Rich ...
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Hansson, Lotta
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Österborg, Ander ...
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Mellstedt, Håkan
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visa färre...
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