Abstract
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 Fcγ receptors (FcγRs) and thus could act as effector cells within the context of antibody therapy. IFNγ 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 IFNγ up-regulated the M1-related markers CD86 and HLA-DR as well as FcγRIa. This corresponded to enhanced FcγR-mediated cytokine production as well as rituximab-mediated phagocytosis of CLL cells. In addition, IFNγ down-regulated the expression of CD31, resulting in withdrawal of the survival advantage on CLL cells. These results suggest that IFNγ can re-educate NLCs and shift them toward an effector-like state and that therapies promoting local IFNγ production may be effective adjuvants for antibody therapy in CLL.
Highlights
Nurse like cells (NLCs)3 are tumor-nurturing cells derived from CD14ϩ monocytes in chronic lymphocytic leukemia (CLL) patients
We found that treatment of NLCs with IFN␥ could reprogram them toward a more effector-like phenotype and in such a way that they no longer supported the survival of CLL cells
IFN␥ significantly enhanced the phagocytic ability of NLCs against opsonized sheep RBCs (SRBCs) as well as rituximab-coated CLL cells
Summary
Nurse like cells (NLCs)3 are tumor-nurturing cells derived from CD14ϩ monocytes in chronic lymphocytic leukemia (CLL) patients. 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 Fc␥RIa. This corresponded to enhanced Fc␥R-mediated cytokine production as well as rituximab-mediated phagocytosis of CLL cells.
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