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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 (author)
- Karolinska Institutet
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- Gentilcore, Giusy (author)
- Karolinska Inst, Canc Ctr Karolinska, Dept Oncol & Pathol, Immune & Gene Therapy Lab, Stockholm, Sweden; Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden
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- Heimersson, Kia (author)
- Karolinska Institutet
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- Mozaffari, Fariba (author)
- Karolinska Institutet
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- Näsman-Glaser, Barbro (author)
- Karolinska Institutet
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- Young, Emma (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Richard Rosenquist Brandell
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- Rosenquist, Richard (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Richard Rosenquist Brandell
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- Hansson, Lotta (author)
- Karolinska Institutet
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- Österborg, Anders (author)
- Karolinska Institutet
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- Mellstedt, Håkan (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2016-12-07
- 2017
- English.
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 102:3, s. 562-572
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Keyword
- SURFACE EXPRESSION; PERIPHERAL-BLOOD; CD152 CTLA-4; CLL PATIENTS; B-CLL; EXPANSION; SUBSETS; STAGE; PD-1; LENALIDOMIDE
- Molekylär medicin
- Molecular Medicine
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Palma, Marzia
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Gentilcore, Gius ...
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Heimersson, Kia
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Mozaffari, Farib ...
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Näsman-Glaser, B ...
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Young, Emma
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show more...
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Rosenquist, Rich ...
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Hansson, Lotta
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Österborg, Ander ...
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Mellstedt, Håkan
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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Haematologica
- By the university
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Uppsala University
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Karolinska Institutet