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

• Grant number: 18/08540-8
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2019
• End date: May 31, 2022
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Maria Fernanda Setúbal Destro Rodrigues
• Grantee: Maria Fernanda Setúbal Destro Rodrigues
• Host Institution: Universidade Nove de Julho (UNINOVE). Campus Vergueiro. São Paulo , SP, Brazil
• Associated 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)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PINTO, MARLENE APARECIDA FERREIRA; FERREIRA, CASSIA BOSI RIBEIRO; DE LIMA, BARBARA EVELYN SANTOS; MOLON, ANGELA CRISTINA; IBARRA, ANA MELISSA COPPA; CECATTO, REBECA BOLTES; FRANCO, ADRIANA LINO DOS SANTOS; RODRIGUES, MARIA FERNANDA SETLIBAL DESTRO. Effects of 5-ALA mediated photodynamic therapy in oral cancer stem cells. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, v. 235, p. 10-pg., 2022-09-08. (19/09465-2, 18/08540-8)

CCOPA IBARRA, ANA MELISSA; CECATTO, REBECA BOLTES; MOTTA, LARA JANSISKI; DOS SANTOS FRANCO, ADRIANA LINO; TEIXEIRA DA SILVA, DANIELA DE FATIMA; NUNES, FABIO DAUMAS; HAMBLIN, MICHAEL R.; SETUBAL DESTRO RODRIGUES, MARIA FERNANDA. Photodynamic therapy for squamous cell carcinoma of the head and neck: narrative review focusing on photosensitizers. Lasers in Medical Science, DEC 2021. (18/08540-8)

J.E. BELIZÁRIO. Immunity, virus evolution, and effectiveness of SARS-CoV-2 vaccines. Brazilian Journal of Medical and Biological Research, v. 54, n. 5, 2021-03-15. (18/08540-8)

SIQUEIRA, JULIANA MOTA; HEGUEDUSCH, DANIELE; RODINI, CAMILA OLIVEIRA; NUNES, FABIO DAUMAS; RODRIGUES, MARIA FERNANDA SETUBAL DESTRO. Mechanisms involved in cancer stem cell resistance in head and neck cell carcinoma. CANCER DRUG RESISTANCE, v. 6, n. 1, p. 22-pg., 2023-01-01. (18/08540-8)