Estudo de diferentes protocolos de diferenciação de células dendríticas na ativação de linfócitos T citotóxicos e gama delta em tumores de mama experimental

Abstract

Currently, cancer is one of the major concerns for health agencies, due to its high mortality rate, this cancer is the leading cause of death among female cancers, as well as presenting a high risk of metastasis to organs such as the liver, bones, lungs and brain. Dendritic cells (DCs) emerge as an important tool in antitumor immunotherapy, as they are a heterogeneous population of leukocytes that play an important role in both the induction and regulation of the innate and adaptive immune response, and due to this capacity, they are considered fundamental in inducing the antitumor immune response. Due to these unique characteristics, they have currently been used in immunotherapy against tumors. However, it is essential to develop new protocols for the differentiation and maturation of DCs, to obtain increasingly satisfactory results. In this context, T lymphocytes, especially cytotoxic ones (CD8+) and gamma delta lymphocytes (γδ), have been essential for a good antitumor immune response, since they are activated by DCs. Gamma delta (γδ) T lymphocytes have the ability to secrete important cytokines such as Interleukin 17 (IL-17) and Interferon gamma (IFN-γ) and exert potent cytotoxicity against a wide variety of cancer cells, as well as CD8+ T lymphocytes. Therefore, the objective of the present study is to quantify the presence of cytotoxic T lymphocytes (CD8+) producing IFN-γ and the presence of γδ T lymphocytes producing IL-17 and IFN-γ in different DC differentiation and maturation protocols, designated in this work as protocol 1 (maturation with TNF-α) and protocol 2 (maturation with TNF-α, IL-12 and RANTES). For this, female BALB/c mice were tumor-induced by the 4T1 cell line and subsequently the experimental groups were treated with protocol 1 or protocol 2. Quantification of cytotoxic T lymphocytes and γδ T lymphocytes producing the cytokines IFN-γ and IL- 17 was performed using the flow cytometry technique. As a result, we found a greater number of cytotoxic T lymphocytes producing IFN-γ and γδ T lymphocytes producing the cytokines IFN-γ and IL-17 in animals treated with protocol 2 compared to protocol 1. In conclusion, protocol 2 proved to be more efficient for the maturation of DCs in antitumor treatment and consequently in inducing a more potent tumor immune response.