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: Kimberly A Noonan, Nilanjan Ghosh, Lakshmi Rudraraju, Marilyn Bui, Ivan Borrello
• Journal: Cancer immunology research (Cancer Immunol Res) Vol. 2 Issue 8 Pg. 725-31 (Aug 2014) ISSN: 2326-6074 [Electronic] United States
• PMID: 24878583 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: ©2014 American Association for Cancer Research.

Chemical References

• Carbolines
• IL4R protein, human
• Immunologic Factors
• Interleukin-4 Receptor alpha Subunit
• Phosphodiesterase 5 Inhibitors
• Thalidomide
• Tadalafil
• Dexamethasone
• Lenalidomide
• Clarithromycin

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carbolines (pharmacology, therapeutic use)
• Clarithromycin (administration & dosage)
• Dexamethasone (administration & dosage)
• Humans
• Immune Tolerance (drug effects)
• Immunologic Factors (administration & dosage)
• Interleukin-4 Receptor alpha Subunit (immunology)
• Lenalidomide
• Male
• Middle Aged
• Multiple Myeloma (drug therapy, immunology)
• Myeloid Cells (drug effects, immunology)
• Phosphodiesterase 5 Inhibitors (pharmacology, therapeutic use)
• T-Lymphocytes (drug effects, immunology)
• Tadalafil
• Thalidomide (administration & dosage, analogs & derivatives)