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Clinical Pharmacology

The Use of TLR7 and TLR8 Ligands for the Enhancement of Cancer Immunotherapy

^aVaccine & Infectious Disease Institute (VIDI), Laboratory of Experimental Hematology, Faculty of Medicine, University of Antwerp, Antwerp, Belgium; ^bCenter for Cellular Therapy and Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium

Key Words. TLR7 • TLR8 • TLR ligands • Cancer • Immunotherapy • Vaccine adjuvant

Correspondence: V. F. I. Van Tendeloo, Ph.D., VIDI, Laboratory of Experimental Hematology, University of Antwerp (UA), Antwerp University Hospital (UZA), Wilrijkstraat 10, B-2650 Antwerp, Belgium. Telephone 32-3-8213661; Fax: 32-3-8214456; e-mail: viggo.van.tendeloo{at}uza.be

Received April 16, 2008; accepted for publication July 14, 2008; first published online in THE ONCOLOGIST Express on August 13, 2008.

Disclosure: The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors, planners, independent peer reviewers, or staff managers.

The importance of Toll-like receptors (TLRs) in stimulating innate and adaptive immunity is now well established. In view of this, TLR ligands have become interesting targets to use as stand-alone immunotherapeutics or vaccine adjuvants for cancer treatment. TLR7 and TLR8 were found to be closely related, sharing their intracellular endosomal location, as well as their ligands.

In this review, we describe the agonists of TLR7 and TLR8 that are known so far, as well as their contribution to antitumor responses by affecting immune cells, tumor cells, and the tumor microenvironment. The major benefit of TLR7/8 agonists as immune response enhancers is their simultaneous stimulation of several cell types, resulting in a mix of activated immune cells, cytokines and chemokines at the tumor site. We discuss the studies that used TLR7/8 agonists as stand-alone immunotherapeutics or cancer vaccine adjuvants, as well as the potential of TLR7/8 ligands to enhance antitumor responses in passive immunotherapy approaches.

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