Reprogramming Nurse-like Cells with Interferon to Interrupt Chronic Lymphocytic Leukemia Cell Survival

Nurse-like cells (NLCs) play a central role in chronic lymphocytic leukemia (CLL) because they promote the survival and proliferation of CLL cells. NLCs are derived from the monocyte lineage and are driven toward their phenotype via contact-dependent and -independent signals from CLL cells. Because of the central role of NLCs in promoting disease, new strategies to eliminate or reprogram them are needed. Successful reprogramming may be of extra benefit because NLCs express Fc receptors (FcRs) and thus could act as effector cells within the context of antibody therapy. IFN is known to promote the polarization of macrophages toward an M1-like state that is no longer tumor-supportive. In an effort to reprogram the phenotype of NLCs, we found that IFN up-regulated the M1-related markers CD86 and HLA-DR as well as FcRIa. This corresponded to enhanced FcR-mediated cytokine production as well as rituximab-mediated phagocytosis of CLL cells. In addition, IFN down-regulated the expression of CD31, resulting in withdrawal of the survival advantage on CLL cells. These results suggest that IFN can re-educate NLCs and shift them toward an effector-like state and that therapies promoting local IFN production may be effective adjuvants for antibody therapy in CLL.