Title:Recent Findings on the Application of Toll-like Receptors Agonists in Cancer Therapy
Volume: 24
Issue: 19
Author(s): Martina Mikulandra, Jasminka Pavelic and Tanja Matijevic Glavan*
Affiliation:
- Laboratory for Personalized Medicine, Rudjer Boskovic Institute, Bijenicka 54, HR- 10000 Zagreb,Croatia
Keywords:
Toll-like receptors, immunity, cancer, therapy, agonists, clinical trials.
Abstract: The immune system’s first line of defense is innate immunity, largely based on a
large family of pattern recognition receptors (PRRs) that recognize evolutionary conserved
molecular motifs on pathogens called pathogen-associated molecular patterns (PAMPs). The
most extensively studied family of PRRs is Toll-like receptors (TLRs), which can trigger
various cellular pathways after ligand stimulation. Their role in cancer is still unresolved as
there are many different studies showing contradictory results. TLRs have been associated
with both tumor progression and immunosuppression as well as with apoptosis and immune
system activation. With their ability to induce apoptotic response and activation of innate and
adaptive immunity, TLRs are an interesting pharmacological target for the development of
anticancer therapy. There are numerous studies including the clinical trials reviewed in this
paper, indicating that TLR agonists, especially combined with other more conventional therapies
such as chemotherapy and radiotherapy, are promising adjuvants or components of newly
developed treatment regimens. Still, the increasing number of studies indicating protumorigenic
consequences of TLR activation in various cancer types and recent reports of the
existence of endogenous TLR ligands, forewarn that more studies on this topic are required
before their inclusion into regular clinical practice.
