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Updated: Sep 30, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Galanin mediates tumor-induced immunosuppression in head and neck squamous cell carcinoma
Marcell Costa de Medeiros1, Min Liu1, Rajat Banerjee1
1Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, 1011 North University Ave, Room 2440, Ann Arbor, MI, 48109-1078, USA.
Purpose:
Galanin receptor 2 (GALR2) plays a significant role in the progression of head and neck squamous cell carcinomas (HNSCC). Since there is virtually no information on immunomodulation mediated by its ligand in the tumor microenvironment, we assessed the effects of galanin on peripheral blood mononuclear cells (PBMCs).
Methods:
After verification of GALR2 expression and it activity in PBMCs we evaluated the effect of galanin and conditioned media from HNSCC cell lines silenced for galanin or antibody-depleted, on proliferation, apoptosis, cytokine expression and activation/differentiation of immune cells.
Results:
We found that galanin alone and as a component of the HNSCC secretome decreased HNSCC cell proliferation and expression of pro-inflammatory cytokines (IFNγ, IL-12, IL-17A, IL-1α, IL-6 and TNF-α), whilst increasing apoptosis and expression of pro-tumoral cytokines/growth factors (IL-10, IL-4, PDGF and GM-CSF). T cell activation (using CD69 as activation marker) and anti-tumoral phenotypes in CD4+ T cells (Th1 and Th17) were found to be suppressed. In vivo, tumor growth was found to be increased in the presence of galanin-stimulated PBMCs. Data from The Cancer Genome Atlas (TCGA) revealed that high expression of galanin was associated with a reduced overall survival of patients with HNSCC.
Conclusion:
Our data indicate that galanin secreted by HNSCC cells exhibits immune-suppressive and pro-tumoral effects.
Insights
Galanin, secreted by head and neck cancers, suppresses immune cells and promotes tumor growth. This finding suggests galanin is a potential therapeutic target for improving patient survival in HNSCC.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Galanin receptor 2 (GALR2) is implicated in head and neck squamous cell carcinoma (HNSCC) progression.
- Limited understanding exists regarding galanin's immunomodulatory role within the HNSCC tumor microenvironment.
Purpose of the Study:
- To investigate the immunomodulatory effects of galanin on peripheral blood mononuclear cells (PBMCs).
- To assess galanin's impact on immune cell function and its contribution to HNSCC progression.
Main Methods:
- Verified GALR2 expression and activity in PBMCs.
- Evaluated galanin's effects on PBMC proliferation, apoptosis, and cytokine profiles.
- Assessed galanin's impact on T cell activation and differentiation.
- Utilized conditioned media from HNSCC cell lines with altered galanin expression.
Main Results:
- Galanin decreased HNSCC cell proliferation and pro-inflammatory cytokine expression (IFNγ, IL-12, IL-17A, IL-1α, IL-6, TNF-α).
- Galanin increased apoptosis and promoted pro-tumoral cytokines (IL-10, IL-4, PDGF, GM-CSF).
- Galanin suppressed T cell activation and anti-tumoral phenotypes (Th1, Th17); galanin-stimulated PBMCs enhanced tumor growth in vivo.
- High galanin expression correlated with reduced HNSCC patient survival (TCGA data).
Conclusions:
- Galanin secreted by HNSCC cells exhibits significant immune-suppressive properties.
- Galanin contributes to a pro-tumoral microenvironment, hindering anti-tumor immunity.
- Targeting galanin may represent a novel therapeutic strategy for HNSCC.
