In vitro evaluation of immunological checkpoints in head and neck squamous cells carcinoma treated with low doses of 5-FU and associated GLPS

• Grant number: 20/03617-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2020
• End date: April 30, 2021
• Field of knowledge: Health Sciences - Dentistry - Dental Clinics
• Principal Investigator: Marcela Rodrigues de Camargo
• Grantee: Emmanuelle Nascimento Quagliato
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil

Abstract

Head and neck squamous cell carcinoma (HNSCC) is currently the sixth in ranking of malignancies in the world and frequently the patients suffer with tumor recurrence and metastasis. Highlighted as the main responsible for metastases, the specific group of cancer stem cells, are known for their high rates of cellular proliferation and self-renewal. In previous studies of the group, the treatment of tongue squamous cell carcinoma (SSC-9) with low doses of 5-flouroracil (5-FU) associated with GLPS (polysaccharides of the Ganoderma lucidum mushroom) was able to reduce cell proliferation, change spheres and colonies formation (characteristics of CSCs) and also inhibit cancer cells migration in vitro. Treatment with 5-FU is a therapy already well established in the HNSCC, however the polysaccharides of G. lucidum have several immunomodulatory activities that involve both humoral and cellular immunity, showing antiangiogenic and antiproliferative activities. Considering that the tumor microenvironment is characteristically immunosuppressive, the objective of this study is to verify whether the association of GLPS with 5-FU is able to immunomodulate this microenvironment to an effective antitumor response by analyzing the expression of immune checkpoints (HLA and PD-L1) and the release of immunosuppressive and immunostimulating cytokines (TNF-±, VEGF, IL-2, IFN-³ and IL-12) of SCC-9 treated cells.