Modulation of adaptive immunity by soluble products of head an neack scamous cell carcinoma (HNSCC) cells: a role for tumor-derived galanin?

Author(s)

Marcell Costa de Medeiros

• Document type: Doctoral Thesis
• Press: Araraquara. 2016-05-31.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Odontologia. Araraquara
• Defense date: 2016-03-31
• Advisor: Carlos Rossa Junior

Abstract

Squamous cell carcinoma of head and neck (HNSCC) is a cancer characterized commonly by local/regional invasion of poor prognosis when diagnosed in advanced stages and are associated with local or systemic immunosuppression. The survival rate for advanced cases is below the breast or prostate cancer, and treatment usually causes severe morbidity. The response to the treatment is highly variable among patients even in the early stages of the disease, despite the treatment implemented following the current standard care. Thus, there is great need to identify biomarkers that indicate an aggressive phenotype and can provide useful information on the development of new target therapies. Our hypothesis was that secreted products by HNSCC cells or direct contact with immune cells can induce a modulation in order to cause tumor evasion of the immune response. We note that the literature shows several studies where tumor cells exert immunosuppressive effect in different cell types of the immune response. The stimulation of PBMC with conditioned medium (CM) of HNSCC cells induced a decrease in proliferation, and modulates a polarization toward anti-inflammatory phenotypes and in co-culture of HNSCC and PBMC pre-treatead with CM caused advantage to tumor cells. Finally we evaluate a possible biomarker, galanin, in modulating the immune response. The absence of galanin induced higher levels of proliferation as well a more bias towards proinflammatory phenotypes. Increase of galanin expression showed a significant escape mechanism of tumor cells from the surveillance of the immune cells, enhancing the proliferation, migration and survival of HNSCC cells. In fact, the tumor microenvironment uses mechanisms that cause immunosuppression, facilitating the growth and progression of cancer. (AU)

• FAPESP's process: 14/06472-4 - Modulation of adaptive immunity by soluble products of HNSCC cells: a role for tumor-derived galanin?
• Grantee: Marcell Costa de Medeiros
• Support Opportunities: Scholarships in Brazil - Doctorate