Exhausting T cells in CLL

Blood (Impact Factor: 10.45). 02/2013; 121(9):1485-6. DOI: 10.1182/blood-2013-01-475939
Source: PubMed


In this issue of Blood, Riches and colleagues provide an in-depth characterization of T cells and particularly CD8+ T cells from patients with chronic lymphocytic leukemia (CLL). They demonstrate that CD8+ T cells exhibit defects in proliferation, cytotoxicity, and increased expression of inhibitory receptors and thus exhibit features of T-cell exhaustion.

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    ABSTRACT: The role of T-cells in the pathogenesis of chronic lymphocytic leukemia has recently gained much attention due to the importance of the constant interaction between neoplastic B-cells with microenvironment substratum and T-cells. It is believed that these interactions modulate the clinical course of the disease, mainly through the regulation of the expansion, differentiation, and survival of chronic lymphocytic leukemia B-cells. Importantly, this crosstalk may also change the number, function, and memory phenotype of normal T-cells, thereby altering the amplitude and/or efficiency of adaptive immunity in chronic lymphocytic leukemia patients. The present study presents an overview on important aspects of this immunological crosstalk, particularly on the abnormalities of chronic lymphocytic leukemia B-cells and the alterations in normal T-cells, with focus on the CD4 memory T-cell compartment that could offer survival signals to chronic lymphocytic leukemia B-cell clone(s) and contribute to the establishment and progression of the disease. The authors believe that understanding the biological consequences of the interaction between normal T- and neoplastic B-cells in chronic lymphocytic leukemia may allow for improvements in the prognostic information and therapeutic approaches for this disease.
    Revista Brasileira de Hematologia e Hemoterapia 03/2014; 36(1):60-64. DOI:10.5581/1516-8484.20140015
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    ABSTRACT: Inhibitors of the Programmed Cell Death 1: Programmed Cell Death 1 ligand 1 (PD-1:PD-L1) pathway, a central regulator of T cell exhaustion, have been recently shown to be effective for treatment of different cancers. However, clinical responses are mixed, highlighting the need to better understand the mechanisms of action of PD-1:PD-L1, the role of this pathway in immunity to different tumors, and the molecular and cellular effects of PD-1 blockade. Here, we review the molecular regulation of T cell exhaustion, placing recent findings on PD-1 blockade therapies in cancer in the context of the broader understanding of the roles of the PD-1:PD-L1 pathway in T cell exhaustion during chronic infection. We discuss the current understanding of the mechanisms involved in reversing T cell exhaustion, and outline critical areas of focus for future research, both basic and clinical. Copyright © 2015. Published by Elsevier Ltd.
    Trends in Immunology 03/2015; 36(4). DOI:10.1016/ · 10.40 Impact Factor