RESUMO
Dendritic cells (DCs) have been attracting attention in cancer immunotherapy because of their role in inducing and modulating effective immune responses. Besides the direct contact with other cell types and the secretion of cytokines, it is becoming clear that nanovesicles, such as exosomes (Exo), secreted by DCs also have a role in their function. Conversely, tumor-derived Exo carry antigens and have been used as a source of specific stimulus for the immune response against tumors. At the same time, several works have shown that different cells types incorporate DC-derived Exo (DC-Exo), resulting in modifications of their phenotype and function. Since DC-Exo carry many of the immune function-associated molecules of DCs, their incorporation by tumor cells could turn tumor cells into immunogenic targets. We have, therefore, treated human breast adenocarcinoma cells (SK-BR-3) with DCs-Exo and used these to stimulate previously SK-BR-3-primed CD3(+) T-cells. Sensitized T-cells cultured with DC-Exo-treated tumor cells showed a significantly higher percentage of IFN-γ-secreting cells (as measured by ELISPOT), when compared to the frequency of cells responding to non-DC-Exo-treated cells. These data show that the incorporation of DC-Exo by the tumor cells increased their ability to activate T-cells for a possibly more effective response, thus showing that DC-Exo may become another tool in cancer immunotherapy.
RESUMO
Dendritic cells (DCs) are essential for the maintenance of homeostasis in the organism, and they do that by modulating lymphocyte priming, expansion, and response patterns according to signals they receive from the environment. The induction of suppressive lymphocytes by DCs is essential to hinder the development of autoimmune diseases but can be reverted against homeostasis when in the context of neoplasia. In this setting, the induction of suppressive or regulatory T cells contributes to the establishment of a state of tolerance towards the tumor, allowing it to grow unchecked by an otherwise functional immune system. Besides affecting its local environment, tumor also has been described as potent sources of anti-inflammatory/suppressive factors, which may act systemically, generating defects in the differentiation and maturation of immune cells, far beyond the immediate vicinity of the tumor mass. Cytokines, as IL-10 and TGF-beta, as well as cell surface molecules like PD-L1 and ICOS seem to be significantly involved in the redirection of DCs towards tolerance induction, and recent data suggest that tumor cells may, indeed, modulate distinct DCs subpopulations through the involvement of these molecules. It is to be expected that the identification of such molecules should provide molecular targets for more effective immunotherapeutic approaches to cancer.
