Galanin Receptor 2 Cause Immunosuppression and has Immune Subversive Effects

Objectives: Galanin receptor 2 (GALR2) is one of three receptors for Galanin, a peptide that is constitutively expressed in many head and neck squamous cell carcinomas (HNSCC). Expression and activation of GALR2 in tumor cells has been positively correlated with HNSCC progression. Considering that HNSCC has an immunosuppressive phenotype, we evaluated the immunomodulatory effect GALR2 expression by HNSCC cells.
Methods: In the ex vivo experiments, we assessed the correlation between the expression of GALR2 and the presence of CD45+, CD4+ and CD8+ cells using tissue microarrays. In vitro, we evaluated the effect of secreted products (conditioned medium - CM) from HNSCC cells (UM-SCC-1 and UM-SCC-22B) with and without GALR2 overexpression on the proliferation, apoptosis, activation and phenotype of immune cells. In direct co-culture experiments (PBMCs and HNSCC cells) we assessed the immunomodulatory effect of priming immune cells with CM from HNSCC cells with and without overexpression of GALR2.
Results: TMAs analyses showed a correlation of GALR2 expression with worse tumor stages (N-stage, M-stage and Grading), also was related with less expression of immune cell markers (CD45 and CD4). Exposure to CM from GALR2-overexpressing cells decreased immune cell proliferation, but did not affect survival. There were significant decreases in the percentages of active CD8 cells and of Th17 cells when immune cells were exposed to CM from GALR2-overexpressing cells. Immune cells primed with CM from GALR2-overexpressing cells allowed for a greater proliferation and migration of tumor cells in direct co-culture experiments.
Conclusions: GALR2 expression by HNSCC cells had an immunosuppressive effect and may be an important target for immunomodulatory-focused therapies.