TY - JOUR AU - Marzia Palma, AU - Giusy Gentilcore, AU - Kia Heimersson, AU - Fariba Mozaffari, AU - Barbro Näsman-Glaser, AU - Emma Young, AU - Richard Rosenquist, AU - Lotta Hansson, AU - Anders Österborg, AU - Håkan Mellstedt, PY - 2017/02/28 Y2 - 2024/03/28 TI - T cells in chronic lymphocytic leukemia display dysregulated expression of immune checkpoints and activation markers JF - Haematologica JA - haematol VL - 102 IS - 3 SE - Articles DO - 10.3324/haematol.2016.151100 UR - https://haematologica.org/article/view/8007 SP - 562-572 AB - 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