in vitro and in vivo expression of the antimicrobial peptide LL-37 in CLL

PODAZA E.; YAN J.; ALMEJUN B; PALACIOS F; RISNIK D; BORGE M; - GAMBERALE R; CHIORAZZI N; GIORDANO M.

Workshop; XVII International workshop on chronic lymphocytic leukemia; 2017

The maintenance and expansion of CLL B cells depend on signals from the microenvironment of lymphoid tissues. The crosstalk between malignant cells and their milieu is mediated through direct cell contact and soluble factors. LL-37 is a C-terminal peptide proteolytically released from human cathelicidin antimicrobial peptide (CAMP) by neutrophils, macrophages and epithelial cells upon stimulation. LL-37 has a broad spectrum of antimicrobial and immunomodulatory activities, and it was shown to be overexpressed in the tumor microenvironment of colon and pancreatic cancer patients, where it promotes tumor cell growth (Li D et al, Oncotarget 33:2709, 2014; Sainz B et al, Gut April 3 2015). We have previously reported that the exogenous addition of LL-37 to CLL-B cell cultures inhibits spontaneous and drug-induced apoptosis. Here we studied the endogenous expression of LL-37 in CLL. By comparing gene expression profiles of 25 samples from CLL patients and 12 samples from healthy donors, we observed that LL-37 expression is higher in B cells from CLL patients (P=0.013). Moreover, there was significantly more LL-37 in unmutated IgVH (n=10) than in mutated IgVH CLL samples (n=15) (P=0.005). Then, we activated CLL B cells with anti-IgM plus CD40 ligand and evaluated the expression of CAMP mRNA by qRT-PCR at 24 h. We found increased levels of CAMP upon activation (control vs activated B-CLL cells, P