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Immnunotherapy to target cancer stem cell subpopulations in oral squamous cell carcinoma: the role of natural killer cells

Grant number: 18/08540-8
Support type:Regular Research Grants
Duration: May 01, 2019 - April 30, 2021
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Maria Fernanda Setúbal Destro Rodrigues
Grantee:Maria Fernanda Setúbal Destro Rodrigues
Home Institution: Universidade Nove de Julho (UNINOVE). Campus Vergueiro. São Paulo , SP, Brazil
Assoc. researchers:Fabio Daumas Nunes ; José Ernesto Belizario

Abstract

Oral squamous cell carcinoma (OSCC) is a very aggressive malignant neoplasm, associated with high mortality rate. Despite the advances in OSCC treatment, the benefits in relation to OSCC prognosis have been disappointing so far and commonly, patients develop recurrence and resistance to therapy. Recent evidences demonstrated that OSCC contains a rare population of cells, called as Cancer Stem Cells (CSC), which are presented in different phenotypes and are responsible to maintain tumor growth, progression, metastasis and treatment resistance. Thus, CSC target therapies are crucial for the success of cancer treatment. In this context, the Natural Killer (NK) cell-based adoptive immunotherapy has shown to be a powerful therapeutic tool in different malignant neoplasms as recently it was demonstrated that these cells preferentially target the CSC in relation to the bulk of tumor cells that comprise the neoplasm. The aim of this study is to evaluate the potential of NK cell to eliminate the CSC subpopulations with epithelial, mesenchymal and amoeboid phenotypes in OSC as well as to evaluate the cellular and molecular mechanisms involved in the recognition and elimination of the CSC by NK cells in OSCC. To achieve the objectives of this study, OSCC cell lines and the CSC subpopulations (CD44high/ESAlow, CD44high/ESAhigh and amoeboid cells) will be co-cultivated with NK cells isolated from periphery blood of health donors and further submitted to cellular and molecular assays in vitro, including cell cytotoxicity, degranulation assay, colony and sphere formation assay,flow cytometry, apoptosis, gene expression and ELISA. (AU)