scholarly journals Prophylactic dendritic cell vaccination in antitumor immune response and tumor growth in a breast cancer mouse model

2021 ◽  
Vol 10 (13) ◽  
pp. e100101320905
Author(s):  
Jéssica Ferreira Vieira ◽  
Eddie Fernando Candido Murta ◽  
Márcia Antoniazi Michelin
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Dendritic Cell ◽  
Tumor Microenvironment ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Tumor Volume ◽  
Dendritic Cell Vaccination ◽  
Tnf Α ◽  
Ifn Γ

Dendritic cell vaccines have demonstrated promising results for poorly immunogenic tumors, which may promote the generation of better immune responses in the tumor microenvironment. However, the vaccine has little been evaluated as a prophylactic option. Therefore, this study evaluates the influence of prophylactic dendritic cell vaccination on the antitumor immune response in the tumor microenvironment and on tumor growth, in an experimental model with breast cancer induced by 4T1. Therefore, Balb/c mice were separated into a vaccinated group and an unvaccinated group. Dendritic cell vaccine was differentiated and matured ex vivo from bone marrow. During the experimental period, the tumor volumes were checked periodically. The tumors were evaluated for immune cells (helper T lymphocytes and cytotoxic T lymphocytes), helper T cells (Th1, Th2, Th17, and Treg), TNF-α, and IFN-γ synthesis by Th1 and cytotoxic T lymphocytes. The vaccinated group had decreased tumor volume (14.0, 0-131.7) compared to the unvaccinated group (89.59, 0.1250-459.6) (p=0.0421). The Th1, Th2, Th17, Treg, cytotoxic T subtypes, including TNF-α and IFN-γ produced by Th1 and T cytotoxic, showed a significant increase in the vaccinated group, as did the balance of Th1/Th2 and Th1/Treg. The results showed that prophylactic vaccination with dendritic cells showed a considerable antitumor effect in the studied model by promoting an increase in the activation of important cells in the immune response and a reduction in tumor volume. The data provide evidence for timely activation of immune surveillance in the absence of tumor burden.

scholarly journals Influence of Immunotherapy with Autologous Dendritic Cells on Innate and Adaptive Immune Response in Cancer

2013 ◽  
Vol 7 ◽  
pp. CMO.S12268 ◽  
Author(s):  
Bruna F. Matias ◽  
Tânia M. De Oliveira ◽  
Cláudia M. Rodrigues ◽  
Douglas R. Abdalla ◽  
Letícia Montes ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
Dendritic Cell ◽  
B Lymphocytes ◽  
Dendritic Cell Vaccine ◽  
Cell Vaccine ◽  
Enzyme Linked Immunosorbent Assay ◽  
Autologous Dendritic Cell ◽  
Tnf Α ◽  
Ifn Γ

The objective of this study was to evaluate some of the mechanisms involved in the activation of the immune system in patients with advanced-stage cancer (n = 7) who received an autologous dendritic cell vaccine. We examined the immune response mediated by macrophages (CD14+), natural killer cells (CD56+), and B lymphocytes (CD19+) by flow cytometry and assessed the expression of Th1 (IFN-γ, TNF-α, IL-2, and IL-12), Th2 (IL-4), and Treg (TGF-β) cytokines by flow cytometry and an enzyme-linked immunosorbent assay. The CD14+ TNF-α+ population was significantly increased ( P < 0.04) when patients received the vaccine; IL-2 expression in both NK cells and in B lymphocytes was increased after a transient initial increase showed a nearly significant decrease ( P < 0.07 and P < 0.06 respectively), whereas the CD19+ and CD56+ populations did not show significant changes. Dendritic cell-based immunotherapy led to increased secretion of IFN-γ and IL-12 and reduced secretion of TGF-β. In conclusion, it is likely that the autologous dendritic cell vaccine stimulated the immune cells from the peripheral blood of patients with cancer and generally increased the production of Th1 cytokines, which are related to immunomodulatory responses against cancer.

scholarly journals Amplification of Cord Blood-Derived Cytotoxic T Lymphocytes using HL-60 cell Derived Exosomes

2021 ◽  
Author(s):  
Xiangcui Gong ◽  
Zhenghao Li ◽  
HuanHuan Wang ◽  
Dong Li ◽  
Xiuli Ju
Keyword(s):  
T Lymphocytes ◽  
Cord Blood ◽  
Cytotoxic T Lymphocytes ◽  
Leukemia Cell ◽  
Promyelocytic Leukemia ◽  
Leukemia Cell Line ◽  
Control Group ◽  
Tnf Α ◽  
Specific Cytotoxicity ◽  
Ifn Γ

IntroductionDendritic cell (DCs) based cytotoxic T lymphocytes (CTLs) are commonly used in immunotherapy due to their specificity. The selection of appropriate cell origin and tumor antigen is the key point. The objective was to culture DCs and CTLs simultaneously from cord blood, and deliver antigen information using tumor derived exosomes.Material and methodsExosomes were collected from the human promyelocytic leukemia cell line HL-60 using ultracentrifugation. Prepared DCs from adherent cord blood mononuclear cells (MNCs) using SCF, GM-CSF, and IN-4. TNF-α and microRNA removed tumor-exosome were used to induce DCs maturation. DCs matured in the presence of HL-60 cell membrane protein extract or no antigen were set as control. CTLs was cultured from non-adherent MNCs by adding IFN-γ, IL-15, SCF, FLT-3L, anti-CD3, anti-CD28 and IL-2. The CTLs were analyzed by flow cytometry, cytotoxicity experiments and ELISA.ResultsDCs can be obtained from cord blood and express costimulatory molecules. After 15 days, the total number of the cells expanded 26.3 times, and more than 82% of the cells expressed CD3+CD8+ in the most amplified HL-60-Ex-DCs-CTL group. These CD3+CD8+ T cells generated by HL-60-Ex-DCs displayed specific cytotoxicity towards HL-60 and low lethality towards unrelated BALL-1 cells. ELISA results showed that the expressions of TNF-α and IFN-γ in HL-60-Ex-DCs or HL-60mPr-DCs activated CTLs were upregulated compared with the control group.ConclusionsCord blood CTLs generated by HL-60 derived exosome activated DCs displayed specific cytotoxicity towards HL-60 promyelocytic leukemia cells. Therefore cord blood and tumor derived exosomes provided a good source for adoptive immunotherapy.

Anti-Myeloma Effects Induced by Myeloma Idiotype Pulsed Dendritic Cells In Vitro.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5131-5131
Author(s):  
Mei Zhang ◽  
Xiaoran Yin ◽  
Yunya Luo ◽  
Xiu Lin ◽  
Pengcheng He ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Peripheral Blood ◽  
Gm Csf ◽  
Tnf Α

Abstract As the most potent antigen-presenting cells, Dendritic cells (DCs), capable of inducing immune responses from naive T cells, are operative tools for tumor immunotherapy. Derived DCs are extremely effective in capturing and presentation of antigens to T cells and play a key role in the induction of cytotoxic T lymphocytes (CTLs). In vitro culture system containing the combination of GM-CSF, IL-4 and TNF-α cytokine can affect CD14 + progenitor cells from mononuclear cells (MNCs) of peripheral blood (PB) developing into functional DCs, which have enough quantities for application in vitro researches and clinical practices. Multiple myeloma cells(MM)are able to secrete a great quantity of immunoglobulin (Ig) expressing idiotypic antigen called idiotype (Id) in its mutational hotspot. This kind of idiotypic structure regions also expressing on the surface of MM cells are high specific autologous tumor associated antigen (TAA). The combination use of DCs and tumor specific antigen can improve the immunogenicity of MM cells and stimulate specific anti-tumor immunological response effectively, so by using this new kind of DC tumor vaccine, following high dose chemical therapy, the tiny residual pathological changes might be cleared totally in the future. To investigate the specific antitumor immune response induced by Id-pulsed dendritic cells(DCs) in vitro. DCs were generated from peripheral blood monocytes of the multiple myeloma(MM) patients using GM-CSF, IL-4, and TNF-α. pulsed with idiotype protein at the immature stage, DCs could activate T cells to become tumor specific cytotoxic T lymphocytes (CTLs). The morphologic characteristics of those cells were observed with light and electron microscopes. The phenotypic figures were analyzed with FACS analysis. Methy-thiazoly-Tetrazolium (MTT) assay was employed to evaluate the effect of proliferation of autologous T cells and the inhibition rate of CTL on MM cells. DCs precursors in peripheral blood could be induced to typical mature DCs in medium containing GM-CSF, IL-4 and TNF-α. Mature DCs with Id could operatively increase proliferation of the autologous T cells and active naive T cells to become tumor specialized CTLs. Any doses of CTLs had significant inhibition or killing ability on autologous MM cells. These results suggest in suitable cytokine environment, the precursors in peripheral blood of MM patients could be induced to functional DCs, and vaccination with Id-pulsed DCs could induce active antitumor immune response. Multiple cycles of immunization using DC as APC in vitro can be beneficial in generating antigen- specific T cells from normal PBMC, and Id an auto-specific tumor antigen, can be got with ammonium sulfate four-step precipitated method, By digestion of pepsin and affinity chromatography so as to stimulate MM specific immunological responce, and Id-pulsed mature DCs from MM patients can stimulate not only the proliferation of autologous T cells, but also the specific CTL immune response against autologous MM cells. In addition, in vitro immunization may provide an alternative approach to in vivo immunization of MM. We believe that DCs vaccine can bring the breakthrough of therapy to MM in the near future.

scholarly journals The Role of T Lymphocytes in Cancer Patients Undergoing Immunotherapy with Autologous Dendritic Cells

2011 ◽  
Vol 5 ◽  
pp. CMO.S6927 ◽  
Author(s):  
Cláudia M. Rodrigues ◽  
Bruna F. Matias ◽  
Eddie F.C. Murta ◽  
Márcia A. Michelin
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
T Lymphocytes ◽  
Regulatory T Cells ◽  
Cancer Patients ◽  
Cytotoxic T Cells ◽  
Cell Populations ◽  
Tnf Α ◽  
Ifn Γ

Introduction Cancer stems from mutations in specific genes that induce uncontrolled cell proliferation. Dendritic cells (DCs) are important immunologic cells and play a crucial role in the induction of an antitumour response. Patients and Methods We examined the immune response mediated by T lymphocytes, helper T cells, cytotoxic T cells, and regulatory T cells, as well as the cytokines [interleukin (IL)-2, IL-12, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and IL-10], produced by these cell populations, in cancer patients (N = 7) undergoing immunotheraphy with autologous DCs. Results We observed an initial increase in T helper cells (CD4+) expressing IL-2, IFN-γ, IL-12, TNF-α, and IL-10 after initiation of treatment, with statistically significant for the cytokines IL-2, TNF-α and IL-10. A similar significant effect was observed for IL-2-expressing cytotoxic T cells (CD8+). The percentage of total T cells (CD3+) remained elevated throughout immunotherapy. Regulatory T cells (CD25+/FOXP3+) only showed high percentage of their maximum value when analyzed the pretreatment levels, with statistically significant. Conclusion Immunotherapy with DCs stimulated the immune response, as evidenced by an increase in percent fluorescence of most cell populations investigated during the specified treatment period.

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