T cells in chronic lymphocytic leukemia display dysregulated expression of immune checkpoints and activation markers

Marzia Palma, Giusy Gentilcore, Kia Heimersson, Fariba Mozaffari, Barbro Näsman-Glaser, Emma Young, Richard Rosenquist, Lotta Hansson, Anders Österborg, Håkan Mellstedt

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)562-572
Number of pages11
JournalHaematologica
Volume102
Issue number3
DOIs
Publication statusPublished - 28 Feb 2017
Externally publishedYes

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T-Cell Prolymphocytic Leukemia
T-Lymphocytes
CTLA-4 Antigen
B-Cell Chronic Lymphocytic Leukemia
Regulatory T-Lymphocytes

ASJC Scopus subject areas

  • Hematology

Cite this

T cells in chronic lymphocytic leukemia display dysregulated expression of immune checkpoints and activation markers. / Palma, Marzia; Gentilcore, Giusy; Heimersson, Kia; Mozaffari, Fariba; Näsman-Glaser, Barbro; Young, Emma; Rosenquist, Richard; Hansson, Lotta; Österborg, Anders; Mellstedt, Håkan.

In: Haematologica, Vol. 102, No. 3, 28.02.2017, p. 562-572.

Research output: Contribution to journalArticle

Palma, M, Gentilcore, G, Heimersson, K, Mozaffari, F, Näsman-Glaser, B, Young, E, Rosenquist, R, Hansson, L, Österborg, A & Mellstedt, H 2017, 'T cells in chronic lymphocytic leukemia display dysregulated expression of immune checkpoints and activation markers', Haematologica, vol. 102, no. 3, pp. 562-572. https://doi.org/10.3324/haematol.2016.151100
Palma, Marzia ; Gentilcore, Giusy ; Heimersson, Kia ; Mozaffari, Fariba ; Näsman-Glaser, Barbro ; Young, Emma ; Rosenquist, Richard ; Hansson, Lotta ; Österborg, Anders ; Mellstedt, Håkan. / T cells in chronic lymphocytic leukemia display dysregulated expression of immune checkpoints and activation markers. In: Haematologica. 2017 ; Vol. 102, No. 3. pp. 562-572.
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AU - Näsman-Glaser, Barbro

AU - Young, Emma

AU - Rosenquist, Richard

AU - Hansson, Lotta

AU - Österborg, Anders

AU - Mellstedt, Håkan

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