- Marzia Palma1,*,
- Giusy Gentilcore2,
- Kia Heimersson2,
- Fariba Mozaffari2,
- Barbro Näsman-Glaser2,
- Emma Young3,
- Richard Rosenquist4,
- Lotta Hansson5,
- Anders Österborg1 and
- Håkan Mellstedt2
- 1 Karolinska University Hospital;
- 2 Karolinska Institutet;
- 3 Department of Immunology, Genetics and pathology,k Science for Life Laboratory, Uppsala University,;
- 4 Rudbeck Laboratory, Uppsala University;
- 5 Karolinska University Hospital Solna, Department of Hematolgoy
- ↵* Corresponding author; email:
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 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 CLL patients both within 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 pretreated patients. In conclusion, chronic lymphocytic leukemia T cells display increased expression of immune checkpoints, abnormal subset distribution and higher proportion of proliferating cells compared to healthy T cells. Disease activity and previous treatment differently shape the T-cell profile of chronic lymphocytic leukemia patients.
- Received June 14, 2016.
- Accepted November 17, 2016.
- Copyright © 2016, Ferrata Storti Foundation