Treatment of colon cancer cells with 5-fluorouracil can improve the effectiveness of RNA-transfected antitumor dendritic cell vaccine

Author(s)

De Almeida, Carolina V. ; Zamame, Jofer A. ; Romagnoli, Graziela G. ; Rodrigues, Cecilia P. ; Magalhaes, Marianna B. ; Amedei, Amedeo ; Kaneno, Ramon

• Document type: Journal article
• Source: ONCOLOGY REPORTS; v. 38, n. 1, p. 561-568, JUL 2017.
• Web of Science Citations: 4

Abstract

Non-cytotoxic concentrations of selected chemotherapeutic agents amplify the antigen presentation capacity of dendritic cells (DCs) and are able to increase the immunogenicity of the colon cancer cell lineage HCT-116, as previously demonstrated by our group. Since this functional alteration was associated with changes in gene expression, we aimed to evaluate whether transcriptional changes of tumor cells can be transferred to DCs, increasing their ability to induce a specific antitumor response. Therefore, HCT-116 cells were treated with two different concentrations of 5-fluorouracil (5-FU), and their total RNA was transfected into human monocyte-derived DC, which function was evaluated through their ability to stimulate the proliferation of normal allogeneic T lymphocytes (MLR), and to generate cytolytic T cells. The transfected DCs demonstrated an increased percentage of CD83(+), HLA-DR+, CD80(+) and CD86(+) cells. These phenotypical changes were followed by functional improvement demonstrated by the increased capacity of these DC to induce allogeneic T cell proliferation and to generate specific anti-HCT-116 cytolytic T cells, as demonstrated by IFN-gamma production following in vitro challenge with tumor cells. Our results allow us to conclude that treatment of tumor cells with a non-toxic concentration of 5-FU induces immunogenic changes that are transferred to DC by transfection of total RNA. (AU)

• FAPESP's process: 09/18331-8 - Chemoimmunomodulation with antineoplastic agents and generation of dendritic cell vaccine
• Grantee: Ramon Kaneno
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/20494-5 - ANTITUMOR THERAPEUTIC POTENTIAL OF DENDRITIC CELLS SENSITIZED WITH ALLOGENEIC EXOSOMES LOADED WITH PROSTATIC PEPTIDES
• Grantee: Graziela Gorete Romagnoli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 09/16311-0 - Effect of K1 protein from different Kaposi's sarcoma associated herpesvirus/ Human herpesvirus type 8 genotypes in the gene expression of human endothelial cells in vitro
• Grantee: Carolina de Almeida Araujo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 09/18433-5 - Generation of antitumoral vaccines of human dendritic cells pulsed with mRNA from tumor cells pre-treated with antineoplasic agents.
• Grantee: Marianna Bartelega Magalhães
• Support Opportunities: Scholarships in Brazil - Scientific Initiation