The cathelicidin LL-37 regulates the survival and activation of B-CLL cells

PODAZA E.; BORGE M; RISNIK D; ALMEJUN B; COLADO A; CRANCO S.; BURGOS R; SANCHEZ AVALOS J; BEZARES RF; GIORDANO M; GAMBERALE R

Sydney

Workshop; XVI International Workshop on CLL; 2015

The microenvironment in lymphoid tissues plays a key role in maintenance and expansion ofCLL cells. The crosstalk between malignant cells and their milieu is mediated through directcell contact and soluble factors, and several molecules involved in these interactions havebeen identified. The cathelicidin LL-37 is a small cationic peptide released by neutrophils,macrophages and epithelial cells upon stimulation. In addition to its antimicrobial properties,LL-37 shows immunomodulatory and chemotactic effects. Recently it was reported to beoverexpressed in the tumor microenvironment of colon and pancreatic cancer, where itpromotes tumor cell growth (Li D et al, Oncotarget 33:2709, 2014; Sainz B et al, Gut April 32015). In contrast, LL-37 was found to be proapoptotic for proliferating lymphoma B cellsand critical for rituximab-mediated cytotoxicity (Bruns H et al, Sc Trans Med 282:1, 2015).Our aim was to determine if LL-37 can affect CLL cell survival and activation. We found thatculture of CLL-B cells (3 x 106 cells/ml) with LL-37 (2.5-10 M) delayed spontaneous andfludarabine-induced apoptosis in a dose- and time-dependent manner (n=20, p