title: Reprogramming Nurse-like Cells with Interferon γ to Interrupt Chronic Lymphocytic Leukemia Cell Survival.
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.
authors.affiliation: Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210.
authors.forename: Shalini
authors.initials: S
authors.lastname: Gautam
authors.affiliation: Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210.
authors.forename: Kavin
authors.initials: K
authors.lastname: Fatehchand
authors.affiliation: Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210.
authors.forename: Saranya
authors.initials: S
authors.lastname: Elavazhagan
authors.affiliation: Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210.
authors.forename: Brenda F
authors.initials: BF
authors.lastname: Reader
authors.affiliation: Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210; Key Laboratory for Molecular Enzymology and Engineering, Ministry of Education, Jilin University, Jilin 130000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ren
authors.affiliation: Center for Biostatistics, Ohio State University, Columbus, Ohio 43210.
authors.forename: Xiaokui
authors.initials: X
authors.lastname: Mo
authors.affiliation: Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210.
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.affiliation: Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210. Electronic address: tridandapani.2@osu.edu.
authors.forename: Susheela
authors.initials: S
authors.lastname: Tridandapani
authors.affiliation: Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210. Electronic address: butchar.2@osu.edu.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Butchar
mesh_terms: D051940:B7-2 Antigen / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism / Q000473:pathology*; D010587:Phagocytosis; D017452:Receptors, IgG / Q000378:metabolism
chemical_list: D051940:B7-2 Antigen; C489017:FCGR1A protein, human; D006684:HLA-DR Antigens; D017452:Receptors, IgG; D007371:Interferon-gamma
keywords: Fc receptor; cell-cell interaction; interferon; signal transduction; tumor immunology