Pseudonormal Morphology of Salivary Gland Adenoid Cystic Carcinoma Cells Subverts the Antitumor Reactivity of Immune Cells: A Tumour-Cell-Based Initiation of Immune Evasion.

ABSTRACT

INTRODUCTION: Salivary gland adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC) and oral squamous cell carcinoma (OSCC) occurs within the head and neck region. So far immune check point inhibitors failed in ACC. Gipie (CCDC88B) is a microtubule linker protein that activates immune cells. Gipie expressions found in head and neck cancer cells. We hypothesised that the presence of Gipie diminishes anti-tumour reactivity of immune cells towards head and neck cancer. METHOD: To determine the effect of Gipie in oral and salivary gland cancer cells, Gipie was silenced in cancer cells in cancer-immune cells co-culture models and we performed 3D Z series confocal imaging, annexin V and immune activation flow cytometry, proteome profiler and discovery phase proteomics. RESULTS: ACC cells morphed into pseudonormal morphology in immune co-culture models. Silencing Gipie in ACC cells showed significant increase of apoptotic cells and activated natural killer cells, and lowering of regulatory T cells. Other salivary and oral cancer cells showed negligible effect of Gipie. Proteome profiler and proteomics assay confirmed Gipie affecting proliferation mechanism and immune activated proteins in ACC immune co-culture models. CONCLUSION: Overall, we conclude that the presence of Gipie has a confounding role during the ACC-immune cell interaction.