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

PODAZA E.A; BORGE M; RISNIK D; ALMEJUN MB; COLADO A; CRANCO S; FERNANDEZ GRECCO H; CABREJO M; BEZARES FR; GAMBERALE R; GIORDANO M

Sidney

Congreso; International Workshop on Chronic Lymphocytic Leukemia; 2015

The microenvironment in lymphoid tissues plays a key role in maintenance and expansion of CLL cells. The crosstalk between malignant cells and their milieu is mediated through direct cell contact and soluble factors, and several molecules involved in these interactions have been 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 be overexpressed in the tumor microenvironment of colon and pancreatic cancer, where it promotes tumor cell growth (Li D et al, Oncotarget 33:2709, 2014; Sainz B et al, Gut April 3 2015). In contrast, LL-37 was found to be proapoptotic for proliferating lymphoma B cells and 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 that culture of CLL-B cells (3 x 106 cells/ml) with LL-37 (2.5-10 µM) delays spontaneous and fludarabine-induced apoptosis in a dose- and time-dependent manner (n=20, p