Low Concentration of 5-Fluorouracil Increases the Effectiveness of Tumor RNA to Activate Murine Dendritic Cells

Author(s)

de Camargo, Marcela Rodrigues ^[1] ; Gorgulho, Carolina Mendonca ^[1] ; Rodrigues, Cecilia Pessoa ^[2] ; Penitenti, Marcimara ^[3] ; Longo Frederico, Juliana Cristina ^[1] ; Marchesan Rodrigues, Maria Aparecida ^[1] ; Kaneno, Ramon ^[2]

Affiliation

^[1] Sao Paulo State Univ UNESP, Sch Med Botucatu, Dept Pathol, Botucatu, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Inst Biosci Botucatu, Dept Microbiol & Immunol, Botucatu, SP - Brazil

^[3] Hosp Amaral Carvalho, Lab Flow Cytometry Jau, Jau - Brazil

• Document type: Journal article
• Source: CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS; v. 32, n. 8, p. 302-308, OCT 2017.
• Web of Science Citations: 0

Abstract

Aim: Considering the central role of dendritic cells (DCs) on the development of an antitumor immune response, in this study we used a murine model to evaluate how DC transfection with drug-treated tumor cell RNA changes their phenotype, and whether transfection enhances the in vivo effectiveness of a DC-based antitumor vaccine. Materials and Methods: MC-38 colorectal tumor cells were pretreated with the minimum effective concentration of 5-fluorouracil (5-FU), then their total RNA was extracted and transfected into DCs. These DCs were inoculated into C57Bl/6 mice bearing subcutaneous MC-38 tumor. Results: DC transfection with drug-treated tumor RNA increases the percentages of CD40(+) (from 37.6% to 61.4%), CD86(+) (from 39.8% to 53.4%), and major histocompatibility complex class II+ (from 51.2% to 75.3%) cells, whereas significantly increases the in vivo generation of interferon-c producer lymphocytes. Conclusion: These results reinforce our view that treatment of tumor cells with 5-FU induces transcriptional changes that can be transferred to DCs by RNA transfection, enhancing their ability to stimulate an antitumor response. (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: 10/06013-9 - In vivo role of dendritic cell vaccines sensitized with mRNA from MC-38 cells pre-treated with antineoplastic agents at minimum effective doses
• Grantee: Marcela Rodrigues de Camargo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/05258-0 - Immunomodulatory effect of low concentrations of antineoplastic
• Grantee: Juliana Cristina Longo Frederico
• Support Opportunities: Scholarships in Brazil - Master