4.5 Article

Phenotypic profile of dendritic and T cells in the lymph node of Balb/C mice with breast cancer submitted to dendritic cells immunotherapy

Journal

IMMUNOLOGY LETTERS
Volume 177, Issue -, Pages 25-37

Publisher

ELSEVIER
DOI: 10.1016/j.imlet.2016.07.009

Keywords

Breast cancer; Dendritic cells; T lymphocytes; Lymph node; Immune response; Immunotherapy

Categories

Funding

  1. Studies and Projects Funding Body (Financiadora de Estudos e Projetos, FINEP)
  2. Foundation for Research Assistance of the State of Minas Gerais (Fundacao de Amparo a Pesquisa do Estado de Minas Gerais, FAPEMIG)
  3. National Council for Scientific and Technical Development (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, CNPq)
  4. Uberaba Foundation for Teaching and Research (Fundacao de Ensino e Pesquisa de Uberaba, FUNEPU)

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Breast cancer (BC) is the most common malignant neoplasm and the cause of death by cancer among women worldwide. Its development influenced by various mutations that occur in the tumor cell and by the immune system's status, which has a direct influence on the tumor microenvironment and, consequently, on interactions with non-tumor cells involved in the immunological response. Strategies using dendritic cells (DCs) or antigen-presenting cells (APCs), therapeutic mode, in cancer have been developed for some time. The proper interaction between DCs and T cells upon antigen presentation is of greatest importance for an antitumor immune response activation. Thus, various receptors on the surface of T cells must be able to recognize ligands that are located on the surface of APCs. However, little is known about the real behavior and interaction forms of CDs and T cells after vaccination. Due to the crucial importance of DCs in an effective anti-tumor immune response activation and the search for compliant results in inducing this response by immunotherapies with DCs, the phenotypic profile of DCs and T cells in lymph nodes obtained from female Balb/C mice with breast cancer induced by 4T1 cells and DCs treated with vaccines was investigated. We evaluated through flow cytometry based on the surface and intracellular molecules marking; as well as the presence of cytokines and chemokines, IL-2, IL-4, IL-10, IL-12, IFN-y, TNF-a. and TGF-I3 in the supernatant of the culture of Balb/C lymph nodes by ELISA. The results show that the vaccination with DCs, in the maturation parameters used in this study, was able to stimulate the secretion of cytokines such as IFN-gamma and IL-12 and inhibit the secretion of TGF-beta and IL-10 in nodal lymph infiltrates, as well as co-stimulatory activating (CD86) and adhesion molecules in DCs and T cells LFA-1 /ICAM-1 and inhibit the secretion of CTLA-4 present in lymph nodes. Facts that led to aTh1 profile polarization, immuno competent in relation to breast cancer. We indirectly evaluated the interaction between DCs and T cells dependent on the vaccination with DCs in tumor draining lymph nodes, in breast cancer in Balb/C mice and we believe that, this way, we will be able to achieve a model vaccine protocol in the future, based on the correct interaction between cells that enable the induction of anti-tumor effective response. Breast cancer (BC) is the most common malignant neoplasm and the cause of death by cancer among women worldwide. Its development influenced by various mutations that occur in the tumor cell and by the immune system's status, which has a direct influence on the tumor microenvironment and, consequently, on interactions with non-tumor cells involved in the immunological response. Strategies using dendritic cells (DCs) or antigen-presenting cells (APCs), therapeutic mode, in cancer have been developed for some time. The proper interaction between DCs and T cells upon antigen presentation is of greatest importance for an antitumor immune response activation. Thus, various receptors on the surface of T cells must be able to recognize ligands that are located on the surface of APCs. However, little is known about the real behavior and interaction forms of DCs and T cells after vaccination. Due to the crucial importance of DCs in an effective anti-tumor immune response activation and the search for compliant results in inducing this response by immunotherapies with DCs, the phenotypic profile of DCs and T cells in lymph nodes obtained from female Balb/C mice with breast cancer induced by 4T1 cells and DCs treated with vaccines was investigated. We evaluated through flow cytometry based on the surface and intracellular molecules marking; as well as the presence of cytokines and chemokines, IL-2, IL-4, IL-10, IL-12, IFN-y, TNF-a. and TGF-p in the supernatant of the culture of Balb/C lymph nodes by ELISA. The results show that the vaccination with DCs, in the maturation parameters used in this study, was able to stimulate the secretion of cytokines such as IFN-gamma and IL-12 and inhibit the secretion of TGF-beta and IL-10 in nodal lymph infiltrates, as well as co-stimulatory activating (CD86) and adhesion molecules in DCs and T cells LFA-1/ICAM-1 and inhibit the secretion of CTLA-4 present in lymph nodes. Facts that led to aThl profile polarization, immuno competent in relation to breast cancer. We indirectly evaluated the interaction between DCs and T cells dependent on the vaccination with DCs in tumor draining lymph nodes, in breast cancer in Balb/C mice and we believe that, this way, we will be able to achieve a model vaccine protocol in the future, based on the correct interaction between cells that enable the induction of anti-tumor effective response. (C) 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

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