RESUMO
Previous studies have demonstrated that maturation of dendritic cells (DCs) by pathogenic components through pathogen-associated molecular patterns (PAMPs) such as Listeria monocytogenes lysate (LML) or CpG DNA can improve cancer vaccination in experimental models. In this study, a mathematical model based on an artificial neural network (ANN) was used to predict several patterns and dosage of matured DC administration for improved vaccination. The ANN model predicted that repeated co-injection of tumor antigen (TA)-loaded DCs matured with CpG (CpG-DC) and LML (List-DC) results in improved antitumor immune response as well as a reduction of immunosuppression in the tumor microenvironment. In the present study, we evaluated the ANN prediction accuracy about DC-based cancer vaccines pattern in the treatment of Wehi164 fibrosarcoma cancer-bearing mice. Our results showed that the administration of the DC vaccine according to ANN predicted pattern, leads to a decrease in the rate of tumor growth and size and augments CTL effector function. Furthermore, gene expression analysis confirmed an augmented immune response in the tumor microenvironment. Experimentations justified the validity of the ANN model forecast in the tumor growth and novel optimal dosage that led to more effective treatment.
Assuntos
Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Fibrossarcoma/terapia , Imunoterapia Adotiva , Linfócitos T Citotóxicos/imunologia , Animais , Linhagem Celular Tumoral , Proliferação de Células , Células Dendríticas/transplante , Fibrossarcoma/imunologia , Regulação Neoplásica da Expressão Gênica , Humanos , Imunidade/genética , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Modelos Teóricos , Transplante de Neoplasias , Redes Neurais de Computação , Carga Tumoral , VacinaçãoRESUMO
Dendritic cells are important in initiating immune responses; therefore, a range of dendritic cell-based approaches have been established to induce immune response against cancer cells. However, the presence of immunosuppressive mediators such as adenosine in the tumor microenvironment reduces the efficacy of dendritic cell-based cancer immunotherapy. In this study, we investigated whether blockade of the A2A adenosine receptor with a selective antagonist and a CD73 inhibitor may increase the efficacy of a dendritic cell-based cancer vaccine. According to the findings, this therapeutic combination reduced tumor growth, prolonged survival of tumor-bearing mice, and enhanced specific antitumor immune responses. Thus, we suggest that targeting cancer-derived adenosine improves the outcomes of dendritic cell-based cancer immunotherapy.
