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

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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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ASJC Scopus subject areas

  • Hematology

Cite this

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, 102(3), 562-572. https://doi.org/10.3324/haematol.2016.151100