Targeted Oncology

, Volume 13, Issue 5, pp 583–598 | Cite as

Targeting Toll-Like Receptors for Cancer Therapy

  • Marc J. Braunstein
  • John Kucharczyk
  • Sylvia AdamsEmail author
Review Article


The immune system encompasses a broad array of defense mechanisms against foreign threats, including invading pathogens and transformed neoplastic cells. Toll-like receptors (TLRs) are critically involved in innate immunity, serving as pattern recognition receptors whose stimulation leads to additional innate and adaptive immune responses. Malignant cells exploit the natural immunomodulatory functions of TLRs, expressed mainly by infiltrating immune cells but also aberrantly by tumor cells, to foster their survival, invasion, and evasion of anti-tumor immune responses. An extensive body of research has demonstrated context-specific roles for TLR activation in different malignancies, promoting disease progression in certain instances while limiting cancer growth in others. Despite these conflicting roles, TLR agonists have established therapeutic benefits as anti-cancer agents that activate immune cells in the tumor microenvironment and facilitate the expression of cytokines that allow for infiltration of anti-tumor lymphocytes and the suppression of oncogenic signaling pathways. This review focuses on the clinical application of TLR agonists for cancer treatment. We also highlight agents that are undergoing development in clinical trials, including investigations of TLR agonists in combination with other immunotherapies.


Compliance with Ethical Standards


No external funding was used in the preparation of this manuscript.

Conflict of Interest

Marc J. Braunstein, John Kucharczyk, and Sylvia Adams declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

Supplementary material

11523_2018_589_MOESM1_ESM.pdf (924 kb)
ESM 1 (PDF 923 kb)


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© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Medicine, NYU Winthrop HospitalMineolaUSA
  2. 2.Department of MedicineNYU Langone Medical Center, Laura and Isaac Perlmutter Cancer CenterNew YorkUSA

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