title: Pharmacological inhibition of TGFβ as a strategy to augment the antitumor immune response.
abstract: There is considerable evidence suggesting that a variety of malignancies utilize the TGFβ cytokine to evade immune surveillance mechanisms to facilitate tumor growth and metastatic progression. The recently developed large- and small-molecule TGFβ inhibitors have demonstrated antitumor efficacy in several preclinical tumor models. Further investigation has revealed these agents to be critically dependent upon the host's immune system, suggesting that the inhibition of TGFβ may overcome the immunosuppressive tumor microenvironment and, ultimately, augment the antitumor immune response. These findings strongly support combining this strategy with other immunotherapeutic approaches for the treatment of metastatic cancer. This review discusses the immunoregulatory and antitumor properties of these pharmacological inhibitors of TGFβ signaling as either independent agents or in combination with various immunotherapeutic strategies, their potential side effects, as well as additional avenues of research that may be necessary for their eventual clinical application.
authors.affiliation: Department of Internal Medicine, Division of Hematology and Oncology, Duke University Medical Center, 450 Research Drive, Durham, NC 27708, USA. hanks004@mc.duke.edu
authors.forename: Brent A
authors.initials: BA
authors.lastname: Hanks
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morse
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007167:Immunotherapy; D008970:Molecular Weight; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016212:Transforming Growth Factor beta