Gene expression profiling of T cells of CLL patients, stimulated with antiCD3 antibody in presence or not of idelalisib

The aim of the study is to identify genes modulated by idelalisib in T cells of CLL patients, that could suggest an impairment of T cell-mediated immunity caused by the drug. We found 61 genes downregulated by idelalisib in stimulated T cells with Anova p≤0.01 and [FC]≥2 and the most represented categories were chemokines involved in T cell migration (as CXCL9-10-11), inflammatory and T helper cytokines (as IL-2, TNFα, IFNg, IL-13, IL-21), mitogenic signal transducers (as IRF4, STAT1, EGR1-2-3-4) and receptors (as CD69, CD25) commonly induced during activation of T cells. T cells were purified from peripheral blood (Pan T cell Isolation kit, Miltenyi Biotech) of n=4 CLL patients and cultured with the three following conditions: i) ctrl (no treatment/no stimulation), ii) antiCD3 (stimulation with antiCD3 antibody), iii) antiCD3 + ide (pre-treatment with idelalisib followed by antiCD3 stimulation). After 4 hours, total RNAs were extracted from T cells and gene expression profiles were measured by hybridization on 4X44K Whole Human Genome Microarray (Agilent Technologies). We first identified differentially expressed genes between the three conditions with Anova p≤0.01. Among these, we focused on genes with [FC]≥2 between antiCD3 and antiCD3+ide conditions.