Toll-like receptor 9; CD289 (TLR9)
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Function
- innate immune response to microbial agents.
- detects the unmethylated cytidine-phosphate-guanosine (CpG) motifs present in bacterial DNA
- acts via MyD88 & TRAF6
- NF-kappa-B activation
- cytokine secretion
- inflammatory response
- binds MyD88 via their respective TIR domains
Structure
- belongs to the Toll-like receptor family
- contains 26 LRR repeats (leucine-rich repeats)
- contains 1 TIR domain
Compartment
membrane
Alternative splicing
named isoforms=5
Expression
- expressed in spleen, lymph node, tonsil & peripheral blood leukocytes, especially in plasmacytoid pre-dendritic cells > monocytes, CD11c+ immature dendritic cells, lung, liver
Pharmacology
- TLR9 agonist CMP-001 restores response to pembrolizumab in 22% of patients with PD-L1 therapy resistant melanoma[2]
More general terms
References
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=54106
- ↑ 2.0 2.1 UniProt http://www.uniprot.org/uniprot/Q9NR96.html
- ↑ Bankhead C Drug May Reverse Anti-PD-1 Resistance in Melanoma. Responses in 22% of resistant patients with TLR9 agonist. MedPage Today. April 19, 2018 https://www.medpagetoday.com/meetingcoverage/aacr/72435
Milhem M, et al Intratumoral toll-like receptor 9 (TLR9) agonist, CMP-001, in combination with pembrolizumab can reverse resistance to PD-1 inhibition in a phase Ib trial in subjects with advanced melanoma. American Association for Cancer Research (AACR 2018) Abstract CT144