HLA Ligandome Analysis of Primary Chronic Lymphocytic Leukemia (CLL) Cells Under In VitroLenalidomide Treatment Confirms Lenalidomide as a Suitable Combination Partner for T-Cell Based Immunotherapy

Several studies have proven the positive immunomodulatory effect of lenalidomide, a second-generation derivative of thalidomide, on T-cell responses in CLL, in particular regarding the repair of the immune synapse between CLL and T cells (e.g., Ramsay et al. J Clin Invest2008), as well as the upregulation of costimulatory molecules on CLL cells (e.g., Aue et al. Haematologica2009). Therefore, lenalidomide seems to be a promising combination partner for T-cell based immunotherapy approaches in CLL patients. We recently conducted a study which directly characterized the antigenic landscape of CLL by mass spectrometric analysis of naturally presented HLA ligands and identified a panel of CLL-specific CD4+as well as CD8+T-cell epitopes as suitable targets for T-cell based immunotherapy (Kowalewski et al. PNAS2015). As anti-cancer drugs can have marked effects on the HLA ligandome of tumor cells, it is of great importance to thoroughly characterize and take into account the effects of the immune modulator lenalidomide not only on the effector cells, but also on the antigenic landscape of the target cells.