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: 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.
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