title: Targeting immune suppression with PDE5 inhibition in end-stage multiple myeloma.
abstract: Myeloid-derived suppressor cells (MDSC) play a significant role in tumor-induced immune suppression. Targeting their function could improve antitumor therapies. Previously, we demonstrated that phosphodiesterase 5 (PDE5) inhibition in MDSCs augmented antitumor immunity in murine models. Here, we show how the addition of the PDE5 inhibitor, tadalafil, in a patient with end-stage relapsed/refractory multiple myeloma reduced MDSC function and generated a dramatic and durable antimyeloma immune and clinical response. Strategies targeting MDSC function with PDE5 inhibitors represent a novel approach that can augment the efficacy of tumor-directed therapies.
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland; and.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Noonan
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland; and.
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Ghosh
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland; and.
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Rudraraju
authors.affiliation: H. Lee Moffitt Cancer Center, University of South Florida, Tampa, Florida.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Bui
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland; and iborrell@jhmi.edu.
authors.forename: Ivan
authors.initials: I
authors.lastname: Borrello
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002243:Carbolines / Q000494:pharmacology / Q000627:therapeutic use*; D017291:Clarithromycin / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D007155:Immunologic Factors / Q000008:administration & dosage; D053662:Interleukin-4 Receptor alpha Subunit / Q000276:immunology; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D000068581:Tadalafil; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D002243:Carbolines; C504000:IL4R protein, human; D007155:Immunologic Factors; D053662:Interleukin-4 Receptor alpha Subunit; D058986:Phosphodiesterase 5 Inhibitors; D013792:Thalidomide; D000068581:Tadalafil; D003907:Dexamethasone; D000077269:Lenalidomide; D017291:Clarithromycin