Although chronic lymphocytic leukemia (CLL) is a B cell malignancy, earlier studies have pointed to involvement of T cells in disease progression and tumor growth. Especially exhaustion and functional silencing of T cells has recently been implicated in the pathogenesis of CLL. In this study, we measured the expression levels of inhibitory cell surface receptors associated with T cell exhaustion and senescence (PD-1, 2B4, and CD57) in a set of 92 CLL samples and 7 healthy controls. We observed that T cells expressing inhibitory receptors were increased within the CD4+ and CD8+ T cell subsets and that this increase was associated with advanced RAI stage within the CD8+ subset. While treatment of patients with chemotherapeutic drugs resulted in further increase of these T cells, patients receiving treatment including the immunomodulatory drug lenalidomide showed a decline in the percentage of cells expressing inhibitory receptors, in particular 2B4 and CD57. PD-1+ T cell subsets were still responsive to T cell receptor stimulation in vitro, whereas reactivation of CD57+CD8+ T cells and 2B4+CD4+ T cells was profoundly impeded, pointing to terminal exhaustion. Our results reveal that chemotherapy increases T cell unresponsiveness, which can be partially prevented by a combined treatment with lenalidomide, which is important to consider upon combining chemo- and immunotherapy aiming at reinvigorating functionally silenced T cells.
Find related publications in this database (Keywords)Apoptosis