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Updated: Apr 15, 2026
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Targeting Toll-like receptor 2 inhibits growth of head and neck squamous cell carcinoma
Lovisa Farnebo1,2, Arash Shahangian1,2, Yunqin Lee1,2
1Division of Head and Neck Surgery, Department of Otolaryngology, Stanford University School of Medicine, Stanford, CA, USA.
Abstract:
Infection-driven inflammation has been proposed to be involved in the tumorigenesis of head and neck squamous cell carcinoma (HNSCC). Oral HNSCC is often colonized with microbes such as gram-positive bacteria and yeast, where ligands derived from their wall components have been shown to specifically bind to Toll-like receptor 2 (TLR2). Although TLR2 has been described to be expressed in oral HNSCC, its function has not been well characterized. Here, we show the expression of TLR2 in both HNSCC cell lines and primary patient-derived HNSCC xenograft tumors. Activation of TLR2 with a yeast-derived ligand of TLR2, zymosan, promoted organoid formation in an ex vivo model of tumor growth, while blockade with anti-TLR2 antibodies inhibited organoid formation. Zymosan also induced phosphorylation of ERK and the p65 subunit of NF-κB, which was inhibited in the presence of anti-TLR2 antibodies, indicating that this receptor is functional in HNSCC and that the signaling through these pathways is intact. TLR2 blockade also inhibited growth of human xenografted tumors in immunodeficient mice. In summary, our data show that TLR2 is a functional receptor expressed in human HNSCC that plays a direct pro-tumorigenic role, and that it can be therapeutically targeted with blocking antibodies to reduce tumor growth.
Insights
Toll-like receptor 2 (TLR2) drives head and neck squamous cell carcinoma (HNSCC) growth. Blocking TLR2 with antibodies inhibited tumor development, suggesting it as a potential therapeutic target for HNSCC.
Area of Science:
- Oncology
- Immunology
- Microbiology
Background:
- Infection-induced inflammation is implicated in head and neck squamous cell carcinoma (HNSCC) tumorigenesis.
- Oral HNSCC harbors microbes like bacteria and yeast, whose cell wall components activate Toll-like receptor 2 (TLR2).
- The precise role of TLR2 in HNSCC remains largely uncharacterized.
Purpose of the Study:
- To investigate the expression and function of TLR2 in HNSCC.
- To determine if TLR2 signaling contributes to HNSCC tumor growth.
- To evaluate the therapeutic potential of targeting TLR2 in HNSCC.
Main Methods:
- Assessed TLR2 expression in HNSCC cell lines and patient-derived xenografts.
- Utilized an ex vivo organoid model to study the effects of TLR2 activation (zymosan) and blockade (anti-TLR2 antibodies) on tumor growth.
- Analyzed downstream signaling pathways (ERK, NF-κB) following TLR2 stimulation.
- Investigated the impact of TLR2 blockade on human HNSCC xenograft tumor growth in immunodeficient mice.
Main Results:
- TLR2 is expressed in HNSCC cell lines and patient tumors.
- TLR2 activation by zymosan promoted HNSCC organoid formation, while blockade inhibited it.
- Zymosan induced ERK and NF-κB signaling, which was blocked by anti-TLR2 antibodies.
- TLR2 blockade significantly inhibited the growth of human HNSCC xenografts in mice.
Conclusions:
- TLR2 is a functional receptor in HNSCC.
- TLR2 signaling plays a pro-tumorigenic role in HNSCC development.
- Targeting TLR2 with blocking antibodies represents a promising therapeutic strategy for reducing HNSCC tumor growth.
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