Galanin mediates tumor-induced immunosuppression in head and neck squamous cell carcinoma

• Published in: Cellular oncology (Dordrecht) Vol. 45; no. 2; pp. 241 - 256
• Main Authors: de Medeiros, Marcell Costa, Liu, Min, Banerjee, Rajat, Bellile, Emily, D’Silva, Nisha J., Rossa, Carlos
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-04-2022; Springer Nature B.V
• Subjects: Apoptosis; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Squamous Cell - pathology; CD4 antigen; CD69 antigen; Cell activation; Cell differentiation; Cell proliferation; Cytokines; Galanin; Galanin - metabolism; Galanin - pharmacology; Genomes; Granulocyte-macrophage colony-stimulating factor; Growth factors; Head and neck carcinoma; Head and Neck Neoplasms - genetics; Helper cells; Humans; Immunomodulation; Immunosuppression; Immunosuppression Therapy; Inflammation; Interleukin 10; Interleukin 12; Interleukin 4; Interleukin 6; Leukocytes (mononuclear); Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - pathology; Lymphocytes T; Oncology; Original; Original Article; Pathology; Phenotypes; Receptor, Galanin, Type 2 - genetics; Receptor, Galanin, Type 2 - metabolism; Squamous Cell Carcinoma of Head and Neck; Tumor Microenvironment; Tumors; γ-Interferon; T lymphocytes; Head and neck cancer; Galanin; PBMCs
• ISSN: 2211-3428; 2211-3436
• DOI: 10.1007/s13402-021-00631-y

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.