TLR agonists: our best frenemy in cancer immunotherapy
Open Access
- 8 March 2013
- journal article
- review article
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 93 (6), 847-863
- https://doi.org/10.1189/jlb.1012501
Abstract
Review on the ability of different TLR agonists to orchestrate antitumor immune responses, or promote tumor growth, underscoring the impact of choosing among TLR agonists when applying these therapies in the clinic. Various TLR agonists are currently under investigation in clinical trials for their ability to orchestrate antitumor immunity. The antitumor responses are largely attributed to their aptitude to stimulate APCs such as DCs which in turn, activate tumor-specific T cell responses. However, there is a potential for TLR signaling to occur on cells other than professional APCs that could negate antitumor responses or even worse, promote tumor growth. The impetus for this review is twofold. First, there is accumulating data demonstrating that the engagement of TLRs on different T cell subsets and different cancer types could promote tumor growth or conversely, contribute to antitumor responses. Second, the efficacy of TLR agonists as monotherapies to treat cancer patients has been limited. In this review, we discuss how TLR signaling within different T cell subsets and cancer cells can potentially impact the generation of antitumor responses. Based on evidence from preclinical models and clinical trials, we draw attention to several criteria that we believe must be considered when selecting TLR agonists for developing effective immunotherapeutic strategies against cancer.Keywords
Funding Information
- NCI (1R01CA140917-01)
- Leukemia and Lymphoma Society Translational Research Progam
- U.S. National Institutes of Health Center for Biomedical Research Center Excellence (1P20 RR021970)
- University of Maryland Marlene and Stewart Greenebaum NCI Cancer Center
This publication has 145 references indexed in Scilit:
- Continuous low-dose cyclophosphamide and methotrexate combined with celecoxib for patients with advanced cancerBritish Journal of Cancer, 2011
- Engineering Dendritic Cells to Enhance Cancer ImmunotherapyMolecular Therapy, 2011
- Structure-Based Analysis of Toxoplasma gondii Profilin: A Parasite-Specific Motif Is Required for Recognition by Toll-Like Receptor 11Journal of Molecular Biology, 2010
- TLR4-mediated skin carcinogenesis is dependent on immune and radioresistant cellsThe EMBO Journal, 2010
- Toll-like Receptor 2 Signaling in CD4+ T Lymphocytes Promotes T Helper 17 Responses and Regulates the Pathogenesis of Autoimmune DiseaseImmunity, 2010
- The TLR3 agonist poly(I:C) targets CD8+ T cells and augments their antigen-specific responses upon their adoptive transfer into naïve recipient miceVaccine, 2009
- Whole-cell cancer vaccination: from autologous to allogeneic tumor- and dendritic cell-based vaccinesCancer Immunology, Immunotherapy, 2008
- Negative regulation of Toll-like receptor-mediated immune responsesNature Reviews Immunology, 2005
- Toll-like receptor control of the adaptive immune responsesNature Immunology, 2004
- Toll-like receptors and innate immunityNature Reviews Immunology, 2001