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Toll-like receptors on B-CLL cells: expression and functional consequences of their stimulation

Publikace na 1. lékařská fakulta, Fakulta tělesné výchovy a sportu, 2. lékařská fakulta, 3. lékařská fakulta |
2010

Tento text není v aktuálním jazyce dostupný. Zobrazuje se verze "en".Abstrakt

Toll-like receptor (TLR) stimulation plays a crucial role in the homeostasis of human B cells. We investigated the expression of TLRs 1-9 on the cells of B-cell chronic lymphocytic leukemia (B-CLL) and analyzed the functional consequences of TLR stimulation on leukemic cells.

We showed that B-CLL cells express similar set of TLRs as memory B cells of healthy donors, i.e. TLR-1, TLR-2, TLR-6, TLR-7 and TLR-9.

However, in contrast to memory B cells, B-CLL cells lack TLR-4 expression. Expression of TLRs correlates with their capacity to respond to specific TLR agonists.

At the level of phenotype, ODN2006 (TLR-9 agonist) is the most potent stimulus. B-CLL cells also respond to the stimulation with loxoribine, Pam3CSK4 and MALP-2 (TLR-7, TLR1/TLR2 and TLR2/TLR6 agonists, respectively).

TLR-7 and TLR-9 stimulation induces production of IL-6 and TNF alpha. In 47% of tested patients, treatment with ODN2006, MALP-2 and Pam3CSK4 reduced leukemic cells survival.

Stimulation of B-CLL cells with TLR-9 agonists, loxoribine, MALP-2 and Pam3CSK4 induces significant proliferation. We report that TLR stimulation induces expression of CD38, a negative prognostic marker, on B-CLL cells.

Expression of CD38 is induced by direct stimulation of B-CLL cells through TLR-7 and TLR-9 or CD38 can be induced on B-CLL cells indirectly by a soluble factor induced in non-B-CLL cells after stimulation with TLR-2, TLR-3 or TLR-5 agonists; the nature of this factor remains unknown. Our results argue for cautious evaluation of immunointervention strategies based on the administration of TLR agonists in the treatment of B-CLL as their effects on B-CLL cells may be tumor promoting as well as tumor suppressing.