@article{Marzia Palma_Giusy Gentilcore_Kia Heimersson_Fariba Mozaffari_Barbro Näsman-Glaser_Emma Young_Richard Rosenquist_Lotta Hansson_Anders Österborg_Håkan Mellstedt_2017, place={Pavia, Italy}, title={T cells in chronic lymphocytic leukemia display dysregulated expression of immune checkpoints and activation markers}, volume={102}, url={https://haematologica.org/article/view/8007}, DOI={10.3324/haematol.2016.151100}, abstractNote={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<sup>+</sup> cells and the CD8<sup>+</sup> subset was particularly expanded in previously treated patients. Progressive patients had higher numbers of CD4<sup>+</sup> and CD8<sup>+</sup> cells expressing PD-1 compared to healthy controls, which was more pronounced in previously treated patients (<em>P</em>=0.0003 and <em>P</em>=0.001, respectively). A significant increase in antigen-experienced T cells was observed in patients within both the CD4<sup>+</sup> and CD8<sup>+</sup> subsets, with a significantly higher PD-1 expression. Higher numbers of CD4<sup>+</sup> and CD8<sup>+</sup> cells with intracellular CTLA-4 were observed in patients, as well as high numbers of proliferating (Ki67<sup>+</sup>) and activated (CD69<sup>+</sup>) CD4<sup>+</sup> and CD8<sup>+</sup> 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 (<em>P</em>&lt;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.}, number={3}, journal={Haematologica}, author={Marzia Palma and Giusy Gentilcore and Kia Heimersson and Fariba Mozaffari and Barbro Näsman-Glaser and Emma Young and Richard Rosenquist and Lotta Hansson and Anders Österborg and Håkan Mellstedt}, year={2017}, month={Feb.}, pages={562-572} }