Effect of serum and antioxidants on the immunogenicity of protein kinase C-activated chronic lymphocytic leukemia cells

Abstract

Since the intrinsically poor immunogenicity of chronic lymphocytic leukemia (CLL) cells might be a key factor in allowing them to avoid immune control mechanisms, the development of methods to enhance CLL cell immunogenicity might lead to improved disease control. The ability of CLL cells to stimulate T cells was increased significantly by the protein kinase C (PKC) agonist phorbol myristic acetate (PMA). However, under serum-free conditions, PMA-activated CLL cells died within 48 hours. Antioxidants, such as 2-mercaptoethanol (2-ME), or fetal calf serum could prevent the death of these cells but caused them to enter distinct states of differentiation. In the presence of 2-ME, PMA-activated CLL cells extended dendritic-like protrusions and exhibited increased T-cell stimulatory capacity. In the presence of serum, PMA-activated CLL cells developed fewer dendrites, made less IL-10 and more IL-12 p40 mRNA transcripts, and showed an increased capacity to induce IFN-gamma production by T cells. The effects of serum on the promotion of type 1 immune responses by phorbol ester-activated CLL cells were dominant and correlated with activation of the NF-kappaB signaling pathway. Other PKC agonists, such as Bryostatin-1 and a synthetic Bryostatin analog (Picolog), had similar effects on CLL cells. The observation that CLL cells can acquire features of dendritic cells that promote type 1 immunity may find clinical application in immunotherapeutic strategies for this disease.