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- Title
Chronic lymphocytic leukaemia induces an exhausted T cell phenotype in the TCL1 transgenic mouse model.
- Authors
Gassner, Franz J.; Zaborsky, Nadja; Catakovic, Kemal; Rebhandl, Stefan; Huemer, Michael; Egle, Alexander; Hartmann, Tanja N.; Greil, Richard; Geisberger, Roland
- Abstract
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 TCL1tg 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 in vivo. These results suggest that T cell exhaustion contributes to CLL pathogenesis and that interference with PDCD1/ CD274 signalling holds high potential for therapeutic approaches.
- Subjects
LYMPHOCYTIC leukemia; T cells; PHENOTYPES; TRANSGENIC mice; TUMOR growth; CELL-mediated cytotoxicity; PHYSIOLOGY
- Publication
British Journal of Haematology, 2015, Vol 170, Issue 4, p515
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/bjh.13467