Expression and function of toll like receptors in chronic lymphocytic leukaemia cells.

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Expression and function of toll like receptors in chronic lymphocytic leukaemia

cells.

Marta Muzio, Cristina Scielzo, T S Bertilaccio, Michela Frenquelli, Paolo

Ghia, and Federico Caligaris-Cappio

Br J Haematol, November 19, 2008; .

Department of Oncology, Unit and Laboratory of Lymphoid Malignancies, Istituto

Scientifico San Raffaele and Università Vita-Salute San Raffaele, Milano, Italy.

Mature B-cells can recognize microbial antigens via B-cell-receptor (BCR) in a

specific way and via Toll-like receptors (TLR) in a costimulatory manner. A

wealth of information is gathering on the possible role of antigenic stimulation

in the natural history of Chronic Lymphocytic Leukaemia (CLL). However little is

known regarding the repertoire and function of TLR in CLL cells. The TLR family

includes 10 different transmembrane proteins devoted to recognize specific

pathogen-associated molecular patterns and to alarm immunocompetent cells to

trigger an immune response. Here, we studied fresh leukaemic cells for the

expression pattern of TLR1 to TLR10, NOD1, NOD2 and SIGIRR (also known as TIR8).

CLL cells were found to express several pattern recognition receptors including

TLR1, TLR2, TLR6, TLR10, NOD1 and NOD2. The specific TLR expressed by CLL cells

were functional. Leukaemic cells, upon stimulation with TLR1/2/6 ligands, such

as bacterial lipopeptides, activated the nuclear factor-kappaB signalling

pathway, expressed CD86 and CD25 activation molecules, and were protected from

spontaneous apoptosis. These findings further support the hypothesis that CLL

cells resemble antigen-activated B-cells and suggest a potential role of TLR in

modulating CLL cell response in the context of specific antigen recognition.

PMID: 19036098