Chronic lymphocytic leukaemia induces an exhausted T cell phenotype in the TCL1 transgenic mouse model. (4th May 2015)

• Record Type: Journal Article
• Authors: Gassner, Franz J.; Zaborsky, Nadja; Catakovic, Kemal; Rebhandl, Stefan; Huemer, Michael; Egle, Alexander; Hartmann, Tanja N.; Greil, Richard; Geisberger, Roland
• Is Part Of: British journal of haematology. Volume 170:Number 4(2015:Aug.)
• Page Start: 515
• Page End: 522
• Publication Date: 2015-05-04
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.13467
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh13467-abs-0001"> <title>Summary</title> <p>Although chronic lymphocytic leukaemia (CLL) is a B cell malignancy, earlier studies have indicated a role of T cells in tumour growth and disease progression. In particular, the functional silencing of antigen‐experienced T cells, called T cell exhaustion, has become implicated in immune evasion in CLL. In this study, we tested whether T cell exhaustion is recapitulated in the TCL1^tg mouse model for CLL. We show that T cells express high levels of the inhibitory exhaustion markers programmed cell death 1 (PDCD1, also termed PD‐1) and lymphocyte‐activation gene 3 (LAG3), whereas CLL cells express high levels of CD274 (also termed PD‐ligand 1). In addition, the fraction of exhausted T cells increases with CLL progression. Finally, we demonstrate that exhausted T cells are reinvigorated towards CLL cytotoxicity by inhibition of PDCD1/CD274 interaction <italic>in vivo</italic>.</p> <p>These results suggest that T cell exhaustion contributes to CLL pathogenesis and that interference with PDCD1/CD274 signalling holds high potential for therapeutic approaches.</p> </abstract>